Friday, October 1, 2021

October 1: Johns Hopkins COVID 19 Report

COVID-19 Situation Report

EDUCATIONAL OPPORTUNITIES The Johns Hopkins Center for Health Security provides education and academic training focused on Health Security for students at the Johns Hopkins Bloomberg School of Public Health. For academic year 2022-23, the Center will provide 2 Masters of Public Health scholarships and fund 2 PhD candidates for the Health Security PhD track at the Johns Hopkins Bloomberg School of Public Health. These opportunities are now accepting applications. Find more information and application details here.

EPI UPDATE The WHO COVID-19 Dashboard reports 233.5 million cumulative cases and 4.77 million deaths worldwide as of October 1.

After plateauing since late July and recording slightly fewer than 800 deaths per day, Russia set a new national record this week for daily mortality (816.4), surpassing 800 daily deaths for the first time since the onset of the pandemic. Russia also reported a new single-day record (852 deaths) on September 28. Russia’s daily incidence has been increasing steadily since mid-September, up from approximately 18,000 new cases per day to nearly 22,000 (+22%) over that period. Russia’s highest average daily incidence was 28,500 new cases per day in late December 2020. Russia has fully vaccinated nearly 30% of its population, but daily vaccinations have steadily declined to less than 25% of its record high in mid-July.

Global Vaccination

The WHO reported 6.14 billion cumulative doses of SARS-CoV-2 vaccines administered globally as of September 29. A total of 3.51 billion individuals have received at least 1 dose, and 2.55 billion are fully vaccinated. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline, remaining at or below 30 million doses per day since September 22*. The global trend continues to closely follow the trend in Asia. Our World in Data estimates that there are 3.57 billion vaccinated individuals worldwide (1+ dose; 45.3% of the global population) and 2.65 billion who are fully vaccinated (33.7% of the global population). As we observed previously with 1+ dose coverage, Oceania’s full vaccination coverage (32.3%) is quickly approaching the global average (33.7%). Oceania could surpass this benchmark in the next several days, which would leave Africa (4.4%) as the only continent below the global average. Oceania and Africa were reporting similar full vaccination coverage as recently as late May, but vaccination efforts in Oceania have progressed rapidly over the past several months.

*The average daily doses administered may exhibit a sharp decrease for the most recent data, particularly over the weekend, which indicates effects of reporting delays. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent data.

The WHO’s Regional Office for Africa (AFRO) announced that only 15 African countries surpassed 10% full vaccination coverage by the target date of September 30. The goal was set by the World Health Assembly in May 2021. Despite accounting for 17% of the global population, only 2% of SARS-CoV-2 vaccine doses administered globally have been in Africa, illustrating the magnitude of ongoing disparities in vaccine access. These countries represent nearly one-third of African nations—compared to nearly 90% of high-income countries—but only about 11% of the African population (1.3 billion). Most of the countries that surpassed the 10% benchmark have small populations, and more than half of all African countries are reporting full vaccination coverage of 2% or less. Seychelles and Mauritius remain at the top of African countries in terms of full vaccination coverage, with 72% and 63%, respectively. Morocco surpassed 50% coverage, Tunisia is reporting 32%, and Cape Verde* is reporting nearly 25%. Vaccination progress is accelerating, however, with monthly distributions increasing 10-fold from June to September. The target by the end of 2021 is 40% coverage, but it is unlikely that more than a small handful of African countries will reach that benchmark.

*Or Cabo Verde.

UNITED STATES

The US CDC reports 43.3 million cumulative COVID-19 cases and 694,701 deaths. Daily incidence continues to decline at the national level, down to approximately 106,000 new cases per day, which is the lowest average since early August. Daily mortality appears to have passed a peak and started to decline. While the average decreased over the second half of September—down to 1,476 per day—the single-day total for September 29 was more than 2,000 deaths, the third-highest since February. At the current pace, the US could surpass 700,000 cumulative deaths in the next 4 days*.

*Changes in state-level reporting may affect the accuracy of recently reported data, particularly over the weekend or for states that are reporting mortality by date of death. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent dates.

US Vaccination

The US has administered 393 million cumulative doses of SARS-CoV-2 vaccines. The daily vaccination trend continues to decline from the most recent peak on August 29*, from approximately 850,000 doses per day to slightly more than 600,000. There are 214.3 million individuals who have received at least 1 dose, equivalent to 64.6% of the entire US population. Among adults, 77.3% have received at least 1 dose, as well as 14.6 million adolescents aged 12-17 years. A total of 184.6 million individuals are fully vaccinated, which corresponds to 55.6% of the total population. Approximately 66.9% of adults are fully vaccinated, as well as 11.9 million adolescents aged 12-17 years. The CDC recently updated its vaccination tracking dashboard to include booster doses. To date, 4.03 million individuals have received booster doses, the majority of whom are aged 50 years and older (3.35 million), including 2.50 million aged 65 years and older.

*Due to delays in reporting, estimates for the average daily doses administered are less accurate for the most recent 5 days. The most current average provided here corresponds to 5 days ago.

VACCINE MANDATES Evidence from several states and private companies that have implemented SARS-CoV-2 vaccine mandates shows the requirements are working to boost vaccination rates among healthcare workers and other employees. In California, major health systems reported a statewide mandate helped increase vaccination rates among their employees to 90% or more, and in New York, 92% of hospital and long-term care facility employees have received at least 1 dose of vaccine after a mandate took effect on September 27, an increase of about 10 percentage points over 1 week ago. However, hospitals in New York continue to fear staff shortages. New York Governor Kathy Hochul signed an executive order earlier this week aimed at providing short-term relief to healthcare systems impacted by staff shortages, but no facilities have closed since the mandate went into effect.

Private employer vaccine mandates are becoming more common, but opposition remains. United Airlines announced this week the company would terminate nearly 600 of its 67,000 employees if they continue to refuse to comply with its vaccination requirement. The company, one of the first large US corporations to impose a mandate, said 99% of its workforce is vaccinated and it is working with employees who decide to get vaccinated after the initiation of their termination proceedings. Tyson Foods, which announced a vaccine mandate for employees in August, said this week that 91% of the company’s 120,000 workers are now vaccinated. Tyson’s frontline workers now have until November 1 to get vaccinated or request an exemption, whereas its 6,000 office workers’ deadline is today. Earlier this month, US President Biden announced a federal vaccine mandate for companies with 100 or more employees, to be enforced by the Occupational Safety and Health Administration (OSHA). The US Armed Forces also are requiring vaccinations for active duty personnel. On September 30, a group of 10 plaintiffs, including US Air Force officers and a Secret Service agent, filed a lawsuit seeking an injunction halting federal vaccination requirements, claiming the mandates violate the First Amendment.

SCHOOL MASK POLICIES Children across the US have had a tumultuous start to the new school year, with more than 900,000 students in 44 states having been affected by COVID-19-related closures between August 1 and mid-September. In 2 new analyses published in the US CDC’s Morbidity and Mortality Report (MMWR), the agency adds to the growing evidence that school mask mandates can help prevent COVID-19 outbreaks in classrooms. Using information from 520 US counties, representing 16.5% of the nation’s total counties, researchers found that pediatric COVID-19 case rates rose more sharply in counties without school mask requirements between July 1-September 4, 2021, when compared with counties that had school mask mandates. The daily case rates remained lower in schools requiring masks even after controlling for covariates. Another analysis examined the association between mask policies and school-associated COVID-19 outbreaks in 2 large Arizona counties that returned to in-person, K-12 schooling in late July/early August 2021. The researchers found that schools without mask mandates were 3.5 times more likely to have a school-related COVID-19 outbreak than those that instituted early mask mandates.

Regardless, legal disputes over mask requirements in schools continue in several states. The US government on September 30 filed a formal statement with the federal district court in Austin, Texas, saying the state’s ban on school mask mandates violates the rights of students with disabilities if it prevents them from safely attending public school in-person. In Iowa, the American Academy of Pediatrics (AAP) and its state chapter filed an amicus brief on behalf of a group of parents and disability rights advocates who filed a federal lawsuit against Governor Kim Reynolds seeking to reverse a law prohibiting school boards from imposing mask mandates. The AAP warned that pediatric COVID-19 cases have risen sharply since the beginning of the school year. Legal proceedings over a law in Arizona banning schools from implementing mask requirements are ongoing, with the state Supreme Court on September 29 setting a briefing schedule to hear arguments. And in Michigan, several local health departments are working to understand language that appears to ban school mask mandates contained within the state’s budget signed this week by Governor Gretchen Whitmer. Although she issued a statement saying a provision that strips state funding from local health departments with school mask mandates is unconstitutional, some districts are rescinding mask requirements over fear of lawsuits.

VACCINE EFFICACY & EFFECTIVENESS REVIEW Researchers from Johns Hopkins University (US) led a systematic review of the efficacy and effectiveness of existing SARS-CoV-2 vaccines. The study (preprint) evaluated clinical trial and observational data for all vaccines that submitted applications for Emergency Use Listing (EUL) from the WHO by August 15, 2021, including data published in peer-reviewed journals and via preprint servers, government public health and regulatory websites and databases, news media, and manufacturers’ websites. The researchers accounted for differences in study population, case definition, follow-up duration, presence of variants of interest or concern (VOIs/VOCs), epidemiological situation (eg, degree of community transmission), and study design.

The study included 24 vaccine products, including multiple vaccine platform technologies, of which 13 had published Phase 3 clinical trial results or data and 6 had received an EUL from the WHO. The researchers provide an overview of the available data and highlight outstanding gaps, including specific types of analysis (eg, effectiveness in previously infected individuals, efficacy/effectiveness against the Gamma variant) and individual products (eg, Sputnik V. Sinopharm-Beijing). Of the 24 products, Phase 3 clinical trial data were available for 15, but only 9 had been subjected to peer review. The researchers also include a set of figures that illustrate the timing of Phase 3 clinical trials in the context of the daily COVID-19 incidence in various countries, which can affect the quality of study data and the duration of clinical trials. Overall, the vaccines currently in use have demonstrated high efficacy/effectiveness against symptomatic COVID-19 disease, severe disease, and death, and analysis exists that also shows some degree of protection against infection. The results vary between products, but among those with available estimates, the efficacy/effectiveness against symptomatic disease was greater than 65% for all of them (and none of the confidence intervals fell below 50%).

ADDITIONAL VACCINE DOSE SAFETY People who received a third dose of an mRNA SARS-CoV-2 vaccine experienced similar adverse events compared with the second dose, according to a report published September 28 in the US CDC’s Morbidity and Mortality Weekly Report (MMWR). Individuals with moderate-to-severe immune-compromising conditions became eligible for an additional dose on August 12, when the US FDA amended the Emergency Use Authorizations (EUAs) for both the Pfizer-BioNTech and Moderna vaccines. The report’s data come from voluntary V-SAFE registrants who completed check-ins for all 3 doses. According to data from 12,591 vaccinees who recorded information for a third dose from August 12-September 19, 2021, 79.4% reported local reactions compared to 77.6% of individuals after a second vaccine dose. Systemic reactions were reported by 74.1% of people after a third dose compared with 76.5% after the second dose. The most frequently reported symptoms included injection site pain, headache, and fatigue, and most commonly occurred the day after vaccination. Overall, no unexpected patterns of side effects were reported among more than 22,000 individuals who received a third vaccine dose and reported to V-SAFE between August 12 and September 19, and their recorded symptoms were categorized as mild or moderate. 

PREGNANCY & VACCINATION The US CDC issued a Health Alert Network (HAN) advisory recommending urgent action aimed at vaccinating pregnant individuals against SARS-CoV-2. The advisory encourages those who are pregnant, recently pregnant (including lactating individuals), who are trying to become pregnant, or who may become pregnant in the future to get vaccinated. The advisory comes after the highest reported number of COVID-19-related deaths in pregnant people (n=22) occurred in August 2021, the agency noted, with more than 125,000 laboratory-confirmed cases and 22,000 hospitalizations among pregnant people since January 2020. A similar directive was issued last month, but this is one of the agency’s strongest recommendations yet for pregnant individuals. Vaccination coverage among pregnant individuals remains low, at 32%, but varies by race/ethnicity. The lowest rate for fully vaccinated pregnant persons is among non-Hispanic Black individuals at 17%, followed by Hispanic or Latino individuals at 27%. Asian pregnant individuals have the highest rate of vaccination at 47%. Non-Hispanic White individuals and those in the ‘other’ category fall in at 35% and 32%, respectively.

LONG COVID Ongoing studies are helping to better characterize and determine the prevalence of so-called long COVID, also known as post-acute sequelae of SARS CoV-2 infection (PASC). In a study published in PLOS Medicine, researchers led by scientists with the University of Oxford conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors, primarily in the US, and included 114,449 patients with influenza as a control. The researchers found that nearly 37% of COVID-19 patients studied reported having at least 1 or more features of long COVID between 3 and 6 months after their initial diagnosis, a higher percentage than the 10%-30% reported in previous studies and significantly higher than after influenza. The most commonly reported symptoms included abnormal breathing; fatigue; chest, throat, or other pain; headache; abdominal symptoms; and anxiety or depression. While lingering symptoms occurred more frequently among people who had more severe acute COVID-19, including those who were hospitalized, and older individuals, the researchers stressed that people who had mild disease and children and young adult survivors also experienced long COVID.

In a study published September 29 in JAMA Network Open, researchers interviewed 2,433 COVID-19 patients who were discharged from 2 hospitals in Wuhan, China, between February 12 and April 10, 2020. Notably, 45% of patients reported at least 1 symptom at 1-year follow-up, with the most common symptoms being fatigue, sweating, chest tightness, anxiety, and muscle pain. Patients who experienced more severe COVID-19 cases and who were older were more likely to have at least 3 lingering symptoms. In yet another study, posted to the preprint server medRxiv, researchers found that SARS-CoV-2 infection, even mild cases, could reduce gray matter thickness in the brain, possibly contributing to long-term neurological damage. Taken together, the studies highlight the fact that the health impacts from COVID-19 extend far beyond the acute phase, and contribute more knowledge about the risk of long COVID, for both unvaccinated and vaccinated individuals, that could help identify those at greatest risk, plan necessary ongoing health services support, and help develop treatments for the condition.

COVAX 2022 STRATEGY The governing body for Gavi, The Vaccine Alliance, met this week to discuss its primary objective of expanding routine immunization but also welcomed participation of the Co-Chairs of the AMC Engagement Group and the COVAX Shareholders’ Council to assess the vaccine initiative’s “critical challenges” and make progress toward developing the 2022 COVAX strategy. The Co-Chairs and Board members expressed support for COVAX’s urgent call to lift all SARS-CoV-2 vaccine export restrictions; manufacturers to deliver on their commitments to COVAX with transparency on schedules and supply chains; countries with high vaccination coverage rates to relinquish their place in line to allow more vaccine supply to go to COVAX and low- and middle-income countries (LMICs) in need; and global donations to be expanded, fast-tracked, and standardized. With more than 311 million doses shipped, the Board highlighted the importance of quickly scaling up vaccine deliveries, as supply is significantly increasing. Echoing the results of the meeting, Gavi Board Chair José Manuel Barroso, a former president of the European Commission, writing in an opinion piece published in POLITICO Europe on September 30, called on wealthy countries’ governments and manufacturers to do more to “close today’s unacceptable gap in vaccine equity.”

US PANDEMIC PREPAREDNESS More than 20 stakeholder organizations this week sent a letter to the US Congress urging them to provide at least US$16 billion in pandemic preparedness funding included in a version of the Build Back Better Act passed by the US House Committee on the Budget. The funding would go toward efforts to improve the country’s pandemic defenses, including the ability to produce diagnostics, vaccines, and treatments for known and future biological threats; track and monitor potential outbreaks; provide sufficient medical supplies; improve indoor air quality; and build a stronger public health infrastructure. But as journalist Ed Yong highlights in a piece in The Atlantic, much more will have to be accomplished in order to protect the nation from the next pandemic, or natural disaster, or climate change impact. Most importantly, those efforts must include improving equity—in education, labor wages, food security, healthcare access, and other social factors—in order to buffer against the next crisis.

SOCIAL MEDIA & VACCINE MISINFORMATION YouTube on September 29 announced the video platform is expanding its medical misinformation policies, including new guidelines for any vaccine that is approved and confirmed to be safe and effective by local and global health authorities. Since last year, the Google-owned company has removed more than 130,000 videos for violating its COVID-19 vaccine policies, but the new guidelines extend beyond the current pandemic and apply to videos claiming proven vaccines are not effective; including misinformation about vaccines’ ingredients; or claiming that vaccines cause autism, cancer, or infertility, or that they contain tracking devices. YouTube also announced it is removing several channels associated with high-profile anti-vaccine proponents, including Joseph Mercola, Sherri Tenpenny, and Robert F. Kennedy Jr. There are exceptions to the rules, as YouTube will continue to allow content providing scientific discussions on vaccine policies, clinical trials, or historic vaccine successes and failures, as well as testimony about personal experiences with vaccines, as long as it doesn’t spill over into advocating against vaccines. The expanded guidelines mark a turning point for YouTube, which has shown some hesitancy against broadening its policing of content, and brings its policies more in line with other social media platforms, including Facebook and Twitter. While many of the so-called Disinformation Dozen continue to have active accounts across social media platforms, misinformation researchers hope YouTube’s policies will help staunch the flow of false vaccine information, as videos from the channel often lead to viral posts on Facebook and Twitter. Some researchers warn that anti-vaccine activists will simply move to other, newer platforms that have fewer restrictions, including Telegram or Gab.

ANTIVIRAL TREATMENT & PREVENTIVE TRIALS Pharmaceutical companies are pushing to develop more effective, easily administered therapeutics for COVID-19, some of which are being studied for the prevention of SARS-CoV-2 infection. This morning, Merck announced that its investigational oral antiviral molnupiravir, which is being developed with Ridgeback Biotherapeutics, significantly reduced the risk of hospitalization or death among non-hospitalized adult COVID-19 patients with mild-to-moderate symptoms who were considered high risk due to other health conditions such as obesity, diabetes, or heart disease. Among patients who took a 5-day course of the drug, 7.3% (28/385) were hospitalized or died compared with 14.1% (53/377) of patients who took a placebo, according to the interim analysis of the Phase 3 MOVe-OUT trial. Merck said it will file an application for Emergency Use Authorization (EUA) with the US FDA as soon as possible, as well as filing applications for marketing with regulatory agencies globally. Over the summer, the US government announced plans to purchase 1.7 million courses of molnupiravir from Merck for about US$1.2 billion, pending US FDA authorization or approval. If authorized, the drug would become the first oral medication available to treat COVID-19.

Pfizer announced on September 27 that it has begun a large Phase 2/3 clinical trial—named EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis)—to evaluate its investigational oral antiviral drug candidate PF-07321332, administered with a low-dose of the antiviral ritonavir, for the prevention of SARS-CoV-2 infection. The global trial is a randomized, double-blind, placebo-controlled study that intends to enroll up to 2,660 healthy adult participants who live in the same household as someone with confirmed, symptomatic COVID-19 disease. In a different study, Pfizer is testing the experimental antiviral among non-hospitalized, symptomatic adult COVID-19 patients.

Swiss pharmaceutical company Roche also is reportedly developing similar treatments for COVID-19. So far, the FDA has approved only Gilead’s antiviral Veklury (remdesivir) for the treatment of COVID-19 in hospitalized patients. However, the drug’s intravenous or injection administration presents challenges to widespread use, so the authorization or approval of an effective orally administered COVID-19 treatment or preventive could help to lower the burden of patients on hospitals.

WINTER OLYMPICS Less than 2 months from the end of the 2020 Summer Olympic Games—which took place a year late due to the COVID-19 pandemic—organizers are formulating pandemic countermeasures for the upcoming 2022 Olympic and Paralympic Winter Games, set to take place in February and March in Beijing. This week, the International Olympic Committee announced some spectators will be allowed to attend events, but only if they are from mainland China. Athletes and team members will not be required to be fully vaccinated to attend, but those who are not will be subject to a 21-day quarantine upon arrival in Beijing. Additionally, an Olympics bubble, or “closed-loop management system,” including required daily testing, will be established like it was in Tokyo in order to help improve safety. During this summer’s Games in Tokyo, at least 430 people tested positive for SARS-CoV-2, including athletes, officials, journalists, employees, contractors, and volunteers.

Tuesday, September 28, 2021

September 28: Johns Hopkins COVID 19 Report

COVID-19 Situation Report

EPI UPDATE The WHO COVID-19 Dashboard reports 231.7 million cumulative cases and 4.75 million deaths worldwide as of September 27. Global weekly incidence and mortality continue to decrease for the third consecutive week.

Global Vaccination

The WHO reported 5.92 billion cumulative doses of SARS-CoV-2 vaccines administered globally as of September 27. A total of 3.38 billion individuals have received at least 1 dose, and 2.46 billion are fully vaccinated. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline, down to approximately 30 million doses per day*. The global trend continues to closely follow Asia. Our World in Data estimates that there are 3.52 billion vaccinated individuals worldwide (1+ dose; 44.7% of the global population) and 2.59 billion who are fully vaccinated (32.9% of the global population).

*The average daily doses administered may exhibit a sharp decrease for the most recent data, particularly over the weekend, which indicates effects of reporting delays. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent data.

As we observed previously with 1+ dose coverage, Oceania’s full vaccination coverage (30.8%) is quickly approaching the global average (32.9%). Oceania could surpass this benchmark in the next several days, which would leave Africa (4.2%) as the only continent below the global average. Oceania and Africa were reporting similar full vaccination coverage as recently as late May, but vaccination efforts in Oceania have progressed rapidly over the past several months.

UNITED STATES

The US CDC reports 42.9 million cumulative COVID-19 cases and 686,639 deaths. Daily incidence continues to decline at the national level, down to approximately 115,000 new cases per day, which would be the lowest average since early August. Daily mortality appears to have leveled off at approximately 1,500 deaths per day.

It appears that daily mortality in Florida has continued to increase since late August, when the state changed its COVID-19 mortality reporting policy. The Florida Department of Health shifted from assigning dates to COVID-19 deaths corresponding to the date they were reported to the date of death. This results in lower reports for recent days due to the inherent reporting lag, which can give a false impression of rapidly declining daily mortality. Deaths are then filled in retrospectively on the date of death as they are reported to the state, which can take days or weeks after the death occurs. At the time of the change, we estimated that Florida’s daily mortality was likely greater than 200 deaths per day. Since then, the average increased to at least 363 (September 1), and it has remained greater than 200 from at least August 7 through September 15. Florida’s daily incidence plateaued from approximately August 10-30 before decreasing. If historical trends continue, we can expect to observe a corresponding decrease in daily mortality around this time; however, it could be another several weeks before Florida’s mortality reporting fills in enough for that trend to be evident.

US Vaccination

The US has administered 391 million cumulative doses of SARS-CoV-2 vaccines. The daily vaccination trend continues to decline from the most recent peak on August 29* (approximately 850,000), down to fewer than 600,000 doses per day. There are 213.7 million individuals who have received at least 1 dose, equivalent to 64.4% of the entire US population. Among adults, 77.1% have received at least 1 dose, as well as 14.6 million adolescents aged 12-17 years. A total of 183.9 million individuals are fully vaccinated, which corresponds to 55.4% of the total population. Approximately 66.6% of adults are fully vaccinated, as well as 11.8 million adolescents aged 12-17 years.

*Due to delays in reporting, estimates for the average daily doses administered are less accurate for the most recent 5 days. The most current average provided here corresponds to 5 days ago.

NOVAVAX WHO EMERGENCY USE LISTING APPLICATION On September 23, Novavax announced its submission to the WHO for Emergency Use Listing (EUL) for its SARS-CoV-2 vaccine candidate. This submission was made in partnership with the Serum Institute of India, which will manufacture the vaccine. Novavax is prioritizing access to low- and middle-income countries (LMICs), and it has already submitted regulatory documents to several individual countries including India, the Philippines, and Indonesia. Novavax and the Serum Institute have jointly pledged to provide more than 1.1 billion doses to the COVAX facility, which also targets LMICs. Phase 3 clinical trials are still ongoing in several countries, including Mexico, the UK, and the US, and preliminary analysis estimates strong efficacy against the original strain of the virus as well as multiple variants of concern (VOCs). 

PFIZER-BIONTECH SUBMIT PEDIATRIC PHASE 2/3 DATA Pfizer and BioNTech announced today that they submitted preliminary data from Phase 2/3 clinical trials on pediatric use of their SARS-CoV-2 vaccine to the US FDA. The submission includes data from nearly 2,300 participants ranging from age 5 years to less than 12 years, and the trial tested a regimen of 2 doses of 10μg each—compared to 30μg for the adult formulation. According to a press release from Pfizer, “the vaccine demonstrated a favorable safety profile and elicited robust neutralizing antibody responses” that were comparable to individuals aged 16-25 years. The companies intend to apply for Emergency Use Authorization (EUA)—as and submit applications to the European Medicines Agency and other national regulatory agencies—for this age group in the coming weeks. White House Chief Medical Advisor Dr. Anthony Fauci indicated that vaccinations for this age group could potentially begin before the end of October. The full trial data have not yet been published publicly or subjected to peer review. Phase 2/3 clinical trials are ongoing for younger children—2 years to less than 5 years and 6 months to less than 2 years—who received 2 doses of 3μg each.

PRIOR INFECTION & IMMUNE PROTECTION As we have discussed previously, protection conferred by vaccination has been demonstrated to be better than protection conferred via natural SARS-CoV-2 infection. Two recent studies, however, provide further analysis of the immune response during and following SARS-CoV-2 infection, including possible protection against re-infection. A study from Japan, published in the Journal of Medical Virology, analyzed the IgG and IgM responses against 2 SARS-CoV-2 proteins (N and S1) in 231 COVID-19 patients. The researchers found that mild cases exhibited stronger immune responses (IgM and IgG) against both proteins early after symptom onset than severe or critical cases. As the disease progressed, the IgM and IgG responses increased in severe and critical cases higher and more rapidly than for mild cases. Additionally, the immune responses remained elevated for longer periods of time in patients with severe or critical disease, while they declined more rapidly for patients with mild disease. ELISA analysis demonstrated that a significantly higher proportion of severe and critical patients remained seropositive at 22 days after symptom onset than for mild patients for the S1 protein but not the N protein. The researchers note that lower immune response among mild cases could potentially signal lower levels of neutralizing antibodies and a shorter period of conferred immune protection against re-infection. Further analysis is needed to better characterize the duration and strength of protection, including the role of the innate immune response and memory B and T cells, and any association with disease severity during the initial infection.

A study in rhesus macaques, published in Science Translational Medicine, evaluated the immune response to re-infection with the Alpha and Beta variants of concern (VOCs) following infection with the original strain of SARS-CoV-2. Researchers infected 18 rhesus macaques with the original strain of the virus (WA1/2020) and then exposed them to either the original strain (control), the Alpha variant, or the Beta variant 35 days later. The animals re-infected with the Alpha variant did not exhibit a notable difference in the concentration of breakthrough virus compared to the control group, whereas the animals re-infected with the Beta variant exhibited much higher concentrations of breakthrough virus. Three (3) additional naïve animals were exposed a single time to the Beta variant in order to compare the immune responses to an original infection and a re-infection. Notably, the animals that were re-infected exhibited lower concentrations of virus, and the re-infected animals exhibited increased neutralizing antibody levels after the second infection, compared to the first. These results suggest a boosted immune response conferred by the initial infection. Interestingly, the animals re-infected with the original strain or the Alpha variant exhibited lower neutralizing antibody responses against the Beta variant, whereas the animals re-infected with the Beta variant generated similar neutralizing antibody responses for all 3 variants. This illustrates that natural infection with one variant can provide some, although not complete, protection against re-infection with other variants, including VOCs; however, the degree of protection could be dependent on the strain or variant. The Delta variant, which has become the dominant strain in many countries, was not evaluated in this study, and as we have covered previously, animal models do not always accurately reflect the immune response in humans.

PANDEMIC ORIGINS Origins of the SARS-CoV-2 virus have been at the forefront of international debate since the onset of the COVID-19 pandemic. The WHO’s Scientific Advisory Group on the Origins of Novel Pathogens (SAGO) was created in May 2020 to identify novel pathogens and advise the WHO on technical and scientific considerations regarding their emergence and re-emergence. SAGO recently released a call for international experts to join the group, with an emphasis on increasing global representation and coordination in the effort to identify the origins of SARS-CoV-2. Some studies have linked SARS-CoV-2 virus to other endemic human coronaviruses and identified genetic similarities between SARS-CoV-2 and other coronaviruses. International debate around the origins of SARS-CoV-2 continues, however, with some experts advocating for a revival of scientific investigations in China and elsewhere, to provide additional information regarding various origin scenarios, including zoonotic transmission or laboratory research. Leading WHO infectious disease epidemiologist Dr. Maria Van Kerkhove emphasized that SAGO is not a new fact-finding mission to China. Rather, SAGO advises the WHO on a framework of study to understand the origins of emerging and re-emerging pathogens, and any future missions, to China or elsewhere, will be coordinated directly between the WHO and national governments.

JAPAN EASING COVID-19 RESTRICTIONS Japanese Prime Minister Yoshihide Suga announced yesterday that Japan will lift its nationwide COVID-19 state of emergency on September 30 and begin relax associated restrictions. While Japan will lift many COVID-19 protective measures, it will reportedly implement testing and vaccine passport programs to mitigate risk while facilitating increased social and economic activity. Local governments may continue to recommend voluntary restrictions on businesses, such as reduced hours of operation and alcohol sales at bars and restaurants, after the emergency is lifted. Japan faced a surge in COVID-19 incidence that coincided with the 2020 Summer Olympic and Paralympic Games, but it has receded rapidly in recent weeks.

AFRICA VACCINE HESITANCY In addition to barriers to accessing sufficient SARS-CoV-2 vaccine supply, African countries are also facing challenges with vaccine hesitancy. Dr. John Nkengasong, Director of the Africa CDC, recently commented on a potential link between international travel restrictions in the UK and hesitancy among African populations. The concern stems from the limited list of countries for which travelers arriving in the UK can “qualify as fully vaccinated.” Travelers vaccinated under a UK, EU, or US vaccination program or individuals arriving from a list of 18 countries who can show proof of full vaccination can enter the UK as “fully vaccinated” travelers, with limited restrictions or quarantine or testing requirements. Notably, the list does not include any countries from Africa, which Dr. Nkengasong argues could serve as a disincentive to get vaccinated. If travelers from African countries cannot qualify as fully vaccinated, even with documentation of full vaccination, some individuals may not see value in the vaccination. Similar opposition has been reported in India and other parts of Asia as well as Latin America. Dr Richard Mihigo, an official from the WHO's Africa region, called on countries to develop a cohesive global system for demonstrating vaccination status and lift travel restrictions for vaccinated travelers that are dependent on country.

SOUTHEAST ASIA ECONOMIC IMPACT The COVID-19 pandemic and associated restrictions continue to have long-term negative effects on local, national, and global economies. In Southeast Asia, several major economic forecasts have downgraded their previous projections and warn of slower economic growth in 2021. The Asian Development Bank lowered its previous regional projection from 4.4% to 3.1% growth over the course of 2021, which signals slower economic recovery from the pandemic. Additionally, the bank lowered its growth projections for all national-level economies, with the exception of the Philippines and Singapore, and Singapore is now the only country in Southeast Asia projected to grow its economy by more than 5% in 2021.

Similarly, the World Bank downgraded its economic growth projections for “developing countries in East Asia.” The new 2021 projection for these countries falls from 4.4% growth to just 2.5%, which stands in stark contrast to the projected 8.5% growth in China. Even in countries that are currently exhibiting stronger economic growth, the trend is slowing as COVID-19 surges continue, driven largely by the Delta variant. The report emphasizes that the pandemic is compounding growing inequality in the region, which will have negative impacts on future economic growth.

Following COVID-19 surges tied to Delta variant, some Southeast Asian countries are once again opening borders to allow travel and tourism, including to some population island destinations in the region. Countries are implementing combinations of vaccine mandates and testing requirements in order to allow international travelers to arrive without lengthy quarantines. Some national and local economies rely heavily on tourism to drive their economies, and they have been severely impacted by travel restrictions during the pandemic. Some countries are moving slowly, with initial limits on traveler volume for specific destinations (including some local areas with high vaccination coverage), before expanding. Some countries that limited domestic travel during the pandemic (eg, to remote islands) are also resuming some domestic travel and tourism opportunities.

NEW YORK HEALTHCARE WORKERS The New York Governor Kathy Hochul, signed an executive order on September 27 to address potential worker shortages as the state’s vaccine mandate goes into effect. The executive order allows the Governor to activate the National Guard or bring in healthcare workers from other states to fill critical personnel shortages. Early evidence indicates that thousands of previously unvaccinated healthcare workers showed up to vaccination sites to receive their first dose in the hours before the mandate went into effect. Approximately 5,000 employees remain unvaccinated, which is a sharp decline from 8,000 a week ago. The statewide vaccination coverage for hospital employees is now reported as 92% with at least 1 dose, and the vaccination also increased among nursing home employees, up from 84%to 92%. Despite these encouraging signs, some hospital employees are still threatening to accept being fired rather than get vaccinated. Some of these individuals indicated that they feel betrayed by the hospital system and government, and they do not trust the vaccine, despite widespread evidence of safety and efficacy. Employees who remain unvaccinated could be put on unpaid leave and eventually fired. The CEO of the New York City Health+Hospitals health system reported that all facilities are currently functional and that there are no serious reports of staffing shortages.

US SCHOOL TESTING Inconsistent SARS-CoV-2 testing procedures and requirements at schools across the US are raising concerns with parents and stressing the capacity of the school systems trying to implement them. Even school districts in the same city can have very different testing and isolation standards. In Texas, for example, the San Antonio Independent School District offers weekly testing for all students and staff, which consumes a lot of time and resources, even though only 30% of students are participating in the program. Conversely, nearby Boerne Independent School District offers testing only by appointment, and symptomatic students and staff are not referred for testing or sent home unless they can no longer participate in classroom instruction.

While some school districts are foregoing robust testing programs based on the belief that they are unnecessary, others are unable to implement them due to a lack of resources, including access to test kits and personnel to conduct large numbers of regular tests. In Illinois, the state reported surge of enrollments in its statewide school-based testing program as daily incidence increased across the state and the new school year approached. But because schools enrolled late in the process, most do not yet have the logistics and operational systems in place to implement the testing programs. It can take 3-6 weeks to establish these systems, which has delayed testing in some schools, even after classes have already resumed. The Berkeley (California) Unified School District used state COVID-19 funding as well as its own budget to hire 21 personnel, just to implement its testing program; however, most school districts do not have the funding available to hire new, dedicated staff for testing programs.

US RAPID TEST SHORTAGE A nationwide shortage of SARS-CoV-2 rapid antigen tests has been reported in the US, while capacity for PCR-based tests remains high. PCR tests must be processed by a lab, however, and results can often take between 1-3 days (or longer). Rapid tests and at-home tests may have a slightly lower accuracy than PCR tests, but they can still identify nearly 98% of infectious cases and provide convenient results within 15-20 minutes. The shortage of rapid testing kits means that schools, nursing homes, shelters, and workers that rely on fast testing results to go to work each day or prevent outbreaks among at-risk populations are struggling to access adequate resources. Increased wait times for testing results mean that shelters, clinics, and schools are at increased risk for outbreaks, and workers who require daily testing could be forced to miss work and lose income.

The nationwide shortage of rapid tests may be a function of decreased testing demands and increasing vaccination coverage over the summer. The Delta variant surge and slowing vaccination progress are driving increased demand for rapid tests, and manufacturers have not yet increased production capacity to catch up. Insufficient supply of rapid and at-home tests is driving up testing demand at other locations, including urgent care centers.

The increased demand and supply limitations for rapid tests is driving up the prices of some other testing products. The CARES Act passed in 2020 requires that insurers pay the cost of SARS-CoV-2 testing conducted at out-of-network laboratories. One company, GS Labs, is routinely charging US$380 per test, and insurers argue that the high cost is “price-gouging,” and in some instances, they are refusing the pay. The elevated cost of these tests could result in higher insurance premiums. GS Labs argues that it approached insurers about becoming an in-network provider for reduced costs, but it was generally rejected. The company also cites its excellent service and a high start-up cost as justification for the elevated price for its tests. A representative for the company emphasizes that customers can schedule an appointment for immediate testing and receive results within 15-20 minutes, while many drugstores and pharmacies have no rapid tests available. There are currently several ongoing lawsuits that aim to determine how much insurers have to pay. Increasing the availability of rapid and at-home tests, which typically cost on the order of US$20, would help increase testing access and reduce the need for higher-cost testing options.

Monday, September 27, 2021

Interesting Article Regarding Advantages of Moderna Vaccine

Business Insider

4 charts show why Moderna vaccine recipients may not need boosters as much as people who got Pfizer's vaccine

Hilary Brueck

Mon, September 27, 2021, 11:45 AM

Pfizer and Moderna vaccine vials

Vials of the Pfizer (left) and Moderna (right) COVID-19 vaccines. Hazem Bader/AFP via Getty Images

  • Millions of adults across the US are now eligible for booster shots of Pfizer's vaccine.

  • Federal authorities are still waiting for more data on Moderna and Johnson & Johnson before recommending a boost to those vaccines.

The US is now offering booster doses of Pfizer's COVID-19 vaccine to tens of millions of people who've been fully vaccinated with Pfizer's shots for at least six months.

man in a mask getting his third booster shot of Pfizer vaccine injected into his right arm by a healthcare worker (also masked).

Booster shots began to be administered at the VA Hospital in Hines, Illinois on September 24, 2021. Scott Olson/Getty Images

Booster doses are most recommended for adults age 65 and up, who don't generally have the same kind of strong, lasting immune response to vaccines as younger people.

But there's not yet any federal guidance about whether, or when, people who've gotten Moderna or Johnson & Johnson's COVID-19 vaccines might need a boost.

a healthcare worker holds a syringe inserted into a vial of pfizer's comirnaty vaccine

Booster shots are being offered to some adults in the US who got Pfizer's vaccine, called Comirnaty. Jens Schlueter/Getty Images

More evidence is beginning to emerge suggesting that people on #TeamModerna may not need a booster as much as others, though.

Last week, the Centers for Disease Control and Prevention released data sets from hospitals around the country, which are starting to show that people who've gotten Moderna's vaccine are less likely to be hospitalized than those with Pfizer or Johnson & Johnson.

Another CDC report released earlier in September suggested that Moderna's two-dose vaccine reduced the risk of hospitalization by 93%. For Pfizer, that figure was 88%, and for Johnson & Johnson it was 71%.

Dr. Robert Atmar, who's leading a pivotal COVID-19 booster study at Baylor College of Medicine, says while it "wouldn't surprise me" if J&J recipients get a booster recommendation soon, "for the Moderna, it is an open question."

The protection Moderna's vaccine offers against hospitalization seems to last longer than other brands.

chart showing vaccine effectiveness appears to wane more with pfizer than with moderna after 4 months

CDC ACIP meeting, September 22-23, 2021.

This data, collected from hospitals in 20 cities across the country, suggests that Moderna's vaccine protects people against hospitalization for longer than both Pfizer and Johnson & Johnson.

After four months, Moderna's vaccine remained 92% effective at preventing hospitalizations, while Pfizer's was 77% effective, and J&J's 68%.

One reason why Moderna may be holding up better in long-term protection is because the vaccine dosage is higher.

vaccine effectiveness chart showing slightly lower effectiveness against hospitalizations for pfizer vaccine than for moderna

CDC ACIP meeting, September 22-23, 2021.

Moderna's shot consists of 100 micrograms of mRNA vaccine, while Pfizer's is 30 micrograms. That may mean lighter side effects for Pfizer's shot, but in the long run the protection might not be as strong.

According to a study of hospitals in New York, Minnesota, Wisconsin, Utah, California, Oregon, Washington, Indiana, and Colorado, Moderna's vaccine is triggering far fewer hospitalizations when people aged 65 and older do get sick.

Another possibility is that the four week interval between doses of Moderna is better than the three week waiting time between shots one and two of Pfizer.

vaccine effectiveness against hospitalization lower with pfizer than moderna

CDC ACIP meeting, September 22-23, 2021.

Both vaccines are still great at preventing severe disease and hospitalization, especially in adults under the age of 65.

Still, this data from five veterans affairs medical centers in the US suggests that Moderna's vaccine is superior at protecting elderly adults, with a vaccine effectiveness of 87% against hospitalization in patients aged 65 and up, whereas Pfizer is 77% effective in that same group.

Since the Delta variant took over in the US, both Moderna and Pfizer recipients are getting sick more often. But Moderna's vaccine effectiveness against hospitalization, for people over age 30, is looking slightly stronger - for now.

charts showing vaccine effectiveness against hospitalization remains very high for both vaccines

CDC ACIP meeting, September 22-23, 2021.

These estimates of vaccine effectiveness, broken down by age group, come from data on over 74,000 hospitalizations across 187 hospitals nationwide.

Here, we can see that Moderna has been outperforming Pfizer among adults ages 30-64. From June to August, Moderna's vaccine effectiveness against hospitalization was 99% in the 30-49 year old age group and 91% among 50-64 year olds. Pfizer's vaccine during that same time period was roughly 82% effective among 30-49 year olds, and 84% effective among 50-64 year olds.

But in younger adults, ages 18-29, the two vaccines performed almost identically, with vaccine effectiveness against hospitalization of 82% for Moderna and 85% for Pfizer.

It's tough to know exactly how the arrival of the Delta variant in the spring may be impacting how well vaccines work.

Whichever way you slice the data, all the vaccines are still pretty stellar at their primary job - keeping people alive and out of the hospital. Still, older adults remain more vulnerable to severe COVID-19 outcomes, even when they're vaccinated.

vaccine effectiveness chart showing protection remains high against hospitalization

CDC ACIP meeting, September 22-23, 2021.

This data, taken from more than 250 hospitals across 14 states, combines both the Pfizer and Moderna vaccine effectiveness against hospitalization in a single chart. It shows the vast majority of COVID-19 cases and deaths nationwide are now among unvaccinated people.

"We will not boost our way out of this pandemic," CDC Director Rochelle Walensky said during a White House COVID-19 briefing on Friday. "The most vulnerable are those unvaccinated."

Read the original article on Business Insider