Both the Moderna and Pfizer vaccines are now available for children ages 6 months through 4 to 5 years. I made a table summarizing both of the vaccines which you can see below. Moderna is given in 2 doses spaced 4 weeks apart and Pfizer is given in 3 doses that take 3 months to complete the series. Moderna's dose is 25 mcg and Pfizer's is 3 mcg. Both vaccines result in neutralizing antibodies at similar levels to young adults which are presumably protective. Moderna's efficacy is about 40% against symptomatic disease and Pfizer's study was too small to really evaluate vaccine efficiency against symptomatic disease, but both vaccines protect against severe disease and death. If my child were under age 5, I would chose the Moderna vaccine over the Pfizer vaccine because the child would be protected after just 6 weeks versus about 14 weeks with Pfizer. But, if Moderna were not available, I would have them vaccinated with Pfizer so they could start to be protected as soon as possible.
This week a large study from the Veterans Administration shows that reinfections with COVID are dangerous and that each additional reinfection increases risks of all-cause mortality, hospitalization, and adverse health outcomes in the lungs and in other organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders). The increased risks were seen in people who were unvaccinated, those who had 1 dose of vaccine, and those with 2 or more doses of vaccine prior to the second infection. Eric Topol talks about the dose-dependent reinfection risks in an article called "A Reinfection Red Flag". The new large V.A. study is particularly important in that before Omicron reinfections happened infrequently (about 1%). But, Omicron is very immune evasive and it can dodge our antibodies unless there are a lot of them. Because of this, reinfections with Omicron will be more common. Remember also that BA.1 infections do not protect against reinfection with BA.4 and BA.5.
Cases and hospitalizations are rising throughout western Europe now as the BA.4/5 wave barrels through. We are all tired of COVID and the pandemic, but in order to stop the spread of these very immune evasive variants, it is important to wear masks indoors, to improve air filtration indoors and to get booster doses of vaccine when due. Everyone over age 50 in the United States can get a 4th dose booster and this is even more important as vaccine immunity wanes.
There are 3 articles on Long COVID in children this week. Notable is that the ONS says that 1 in 50 elementary school children and 1 in 20 teens in the UK now have Long COVID. The repercussions of Long COVID on these children's lives could affect them long term.
In good news, Moderna announced that their bivalent vaccine containing mRNA for 2 strains of SARS-CoV-2 (the original virus and Omicron BA.1) caused people to make potent neutralizing antibodies against BA.4 and BA.5. Moderna is asking for FDA approval of this new vaccine and it is expected to be available in the fall. A real-world study from Kaiser Permanente in Southern California shows that Paxlovid worked very well preventing hospitalizations and severe disease in 99% of high risk patients. Paxlovid is a game changer for high risk people but unfortunately a new study shows that the high risk people who live in the most vulnerable areas do not always have great access to Paxlovid because of a lack of health care providers in those areas.
Finally, a new study in the New England Journal of Medicine shows that maternal vaccination is effective in reducing the risk of Covid-19–related hospitalization in infants younger than 6 months of age. COVID vaccination during pregnancy protects both mother and baby.
6/24/22 CNBC: Supreme Court overturns Roe v. Wade, ending 50 years of federal abortion rights https://buff.ly/39P84BL
6/24/22 AP: Democrats vow to help women who must travel for abortions https://buff.ly/3NptUcG
Democratic governors of California, Washington and Oregon will work together.
California state’s budget will include $20 million over three years to help pay for women from other states to get abortions in California. The money will go to nonprofits that help women pay for expenses such as travel, lodging and child care.
Gay and bisexual men urged to get vaccinated if living in Florida, or talk with their healthcare provider about vaccination if traveling to Florida.
Meningococcal vaccine (MenACWY) prevents the infection.
Symptoms can appear suddenly and include high fever, headache, stiff neck, nausea/vomiting, or a dark purple rash. Symptoms can first appear as a flu-like illness, but typically worsen very quickly.
6/23/22 NY Times: Britain Declares National Incident After Poliovirus Found in London Wastewaterhttps://buff.ly/39J0eJV
Health authorities urged anyone who is not fully immunized against poliovirus, particularly young children, to immediately seek vaccines.
Vaccinations started this week for children under age 5 in the U.S.:
6/20/22 American Academy of Pediatrics: COVID-19 Vaccine: Frequently Asked Questions https://buff.ly/3b9gpAt
6/20/22 Brown University School of Public Health: Talking About Covid-19 Vaccines for Children Six Months to Four Years Old by @meganranney @jeremyfaust https://buff.ly/3HFjcNX
6/20/22 My Toddlers Already Had COVID-19. I'm Still Getting Them Vaccinated by @dr_kkjetelina https://buff.ly/3OvmFB5
6/24/22 The Guardian: Covid surges across Europe as experts warn not let guard down https://buff.ly/3Ni1scK
BA.4 and BA.5 wave.
The rolling seven-day average of confirmed new cases is on the rise in Portugal, France, Germany, Italy, Spain, Greece, the Netherlands and Denmark.
Portugal has experienced the most dramatic wave and BA.4 and BA.5 variants had led to significant excess deaths in Portugal.
Hospital admissions in France are up 27% and ICU admissions 17% in a week.
Vulnerable people should get a fourth shot of the vaccine and masks are important in enclosed spaces.
6/24/22 Covid infections rise 20% in England as new Omicron variants (BA.4 and BA.5) spread https://buff.ly/3A30myK
Scotland hit hardest as cases climb 40% to leave 1 in 20 people with COVID.
In England, infections increased across all age groups.
Only 1 in 4 Americans age 50+ have had a 2nd booster.
In people age 50+, compared to unvaccinated people:
81% reduction in death if vaccinated (2 doses) and no boosters
86% reduction in death if had 1st booster (3 doses total)
99% reduction in death if had 2 boosters (4 doses total)
Boosters work to prevent severe disease and death.
6/23/22 NEJM: Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infantshttps://buff.ly/3OFo3RJ
Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age.
Better vaccine effectiveness noted for infants if their mother's received the vaccine after 20 weeks of gestation.
6/23/22 NEJM Ed: Covid-19 Vaccination during Pregnancy — Two for the Price of Onehttps://buff.ly/3OC75U5
Maternal antibodies have been shown to be present in umbilical-cord blood, neonatal blood, and breast milk after maternal Covid-19 vaccination, but the correlation with infant protection from infection was unclear before the Halasa et al study.
The study shows compelling evidence that maternal vaccination is effective in reducing the risk of Covid-19–related hospitalization in infants younger than 6 months of age, a finding that further supports recommendations for Covid-19 vaccination during pregnancy to protect both mother and baby.
Long COVID in Children (3 articles):
6/23/22 UK Office for National Statistics (ONS): COVID-19 Schools Infection Survey, England https://buff.ly/3tUBYvk
Nearly 1 in 50 (1.8%) primary school pupils and nearly 1 in 20 (4.8%) secondary school pupils have Long COVID.
Significantly more secondary school pupils who reported having COVID-19 had experienced loss of smell or taste, cardiovascular symptoms, or systemic symptoms (fever or high temperature) than those who reported not having had COVID-19.
Secondary school pupils in years 7 to 13 with Long COVID were significantly more likely to have a probable mental disorder (28.1%) than those without long COVID (12.3%).
6/23/22 Lancet: Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study https://buff.ly/3u0DgVr
38,152 cases (positive COVID test Jan 2020 to July 2021) and 33,016 controls
COVID cases had higher odds of reporting at least one symptom lasting more than 2 months than controls:
COVID cases age 0-3 years had 1.8x odds of symptoms lasting 2+ months
COVID cases age 4-11 years had 1.2x odds of symptoms lasting 2+ months
COVID cases age 12-14 years had 1.2x odds of symptoms lasting 2+ months
6/23/22 Nature: Long COVID in children and adolescents: a systematic review and meta-analyses https://buff.ly/3tZAShB
Meta-analysis of 21 studies showed the prevalence of long COVID was 25%, and the most prevalent clinical manifestations were mood symptoms (16.5%), fatigue (9.7%), and sleep disorders (8.4%).
Children infected by SARS-CoV-2 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever compared to controls.
6/22/22 Reuters: Nearly 1 in 5 adults who had COVID have lingering symptoms - U.S. studyhttps://buff.ly/3tZncmJ
1 in 5 American adults who had COVID have Long COVID symptoms, according to survey data collected in the first two weeks of June.
Overall, 1 in 13 adults in the United States have long COVID symptoms lasting for three months or more.
Long COVID symptoms range from fatigue, rapid heartbeat, shortness of breath, cognitive difficulties, chronic pain, sensory abnormalities and muscle weakness. They can be debilitating and last for weeks or months after recovery from the initial infection.
Long COVID is more common in younger people and in women.
9.4% of U.S. adult women report long COVID symptoms compared to 5.5% of men.
9% of Hispanic adults have long COVID, higher than non-Hispanic white and Black adults, and more than twice the percentage of non-Hispanic Asian adults.
6/22/22 FT: Moderna calls for approval of two-strain Covid vaccine booster https://buff.ly/3NfnhJX
The Moderna bivalent vaccine containing mRNA for the original strain and for Omicron BA.1 demonstrated a “potent neutralizing antibody response” to BA.4 and BA.5.
The bivalent vaccine elicited 5x increase in neutralizing antibodies to BA.4 and BA.5.
The bivalent vaccine elicited 8x increase in neutralizing antibodies to BA.1.
Studies have shown that previous BA.1 infections do not provide a strong antibody response against BA.4/5.
6/22/22 Preprint: A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptomshttps://buff.ly/3yboeie
Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively.
At home taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals with Long COVID or PASC.
This has the potential to help treat dysautonomia in Long COVID.
New very large study from the Veterans Administration (see below) shows that each additional COVID reinfection negatively affects the cardiovascular system, the kidneys and mental health, and increases the risk of new onset diabetes, causes 3 fold increases in hospitalizations and 2 fold increase in all-cause mortality.
There is the “dose-response” effect of multiple reinfections meaning with additional episodes of Covid, for every outcome there are stepwise increased risks.
Omicron subvariants BA.2, BA.2.12.1, BA.4, and BA.5 have become more and more immune evasive meaning that they can escape our antibodies from vaccination and prior infections including BA.1.
To protect ourselves and others, we should wear N95 or KN95 masks, improve ventilation and air filtration, get booster vaccinations and vaccinate children more. In addition, Dr. Topol recommends working towards pan-coronavirus and nasal vaccines which will be more effective against new variants.
US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855).
Compared to people with first infection, reinfection contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extrapulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders).
The risks were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection.
The risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection.
Risk increased in a graded fashion according to the number of infections.
Figure 5: Cumulative risk and burden of sequelae in people with one, two, and three or more SARS-CoV-2 infections compared to a non-infected control.
6/23/22 BMJ (Liechtenstein): Investigation of the use of a sensor bracelet for the presymptomatic detection of changes in physiological parameters related to COVID-19: an interim analysis of a prospective cohort study (COVI-GAPP) https://buff.ly/3QUMFI6
Ava-bracelet that measured respiratory rate (RR), heart rate (HR), HR variability (HRV), wrist-skin temperature (WST) and skin perfusion at night.
An algorithm identified 68% of COVID-19 positive participants 2 days prior to symptom onset.
6/22/22 CDC MMWR: Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment — California, December 2021–May 2022 https://buff.ly/3QRL45Q
Kaiser Southern California, real world data
Hospitalizations or ER encounters occurred infrequently, representing <1% of Paxlovid-treated patients when administered as an early-stage treatment to persons with mild to moderate COVID-19 cases who are at risk for progression to severe disease.
6/22/22 CDC MMWR: Dispensing of Oral Antiviral Drugs for Treatment of COVID-19 by Zip Code–Level Social Vulnerability — United States, December 23, 2021–May 21, 2022 https://buff.ly/3ngN4GV
Antiviral medications were found to be inequitably prescribed.
Dispensing rates were lowest in high vulnerability zip codes, despite having the largest number of dispensing sites.
Most pharmacies serving as dispensing sites do not have authorized prescribers available on-site or via telemedicine.
6/22/22 NEJM: Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5 https://buff.ly/3OlpFQF
BA.2.12.1, BA.4, and BA.5 subvariants substantially escape neutralizing antibodies induced by both vaccination and infection more than BA.1 or BA.2.
6/21/22 Nature: Drivers of adaptive evolution during chronic SARS-CoV-2 infections https://buff.ly/3Oc0SOY
Immunocompromised people with chronic SARS-CoV-2 infections can have polymorphic viral populations. The virus mutates to evade neutralizing antibodies (i.e. immune evasion).
Extensive genomic monitoring of chronic infections is necessary to further understanding of VOC emergence.
6/21/22 Nature: How COVID infections lasting months could seed dangerous new variants https://buff.ly/3HBGTH6
Tracking SARS-CoV-2 evolution during chronic cases in immunosuppressed patients provides insight into the origins of Omicron and other global variants.
COVID-19 infection lingered for more than seven months in a woman on immune-suppressing drugs to treat a lymphoma relapse in Austria causing relatively mild symptoms, including fatigue and a cough.
Genomic studies were done longitudinally and scientists could see as new mutations happened. Over half of the mutations were also seen in the Omicron variant.
“I don’t think there can be any doubt in anyone’s mind that these are a source of new variants”
