Warning Shots
Florida
A Florida high school held its graduation on July 25th. Shortly after that date, one of those in attendance tested positive for coronavirus. Almost 300 graduates and their families who were in attendance were told to quarantine by the health department.
Indiana
That’s going to be a tough question that is going to get repeated over and over again. As case counts climb across most of the US, it’s going to become more and more likely that any plans will need to be implemented. The New York Times made a great illustration how likely that is based on school size and location based on work by the University of Texas at Austin.
Massachusetts
During the summer school program for special needs children, two teachers and one administrative staff member tested positive for COVID-19. The interim superintendent stated “We knew we were going to experience things like this — that people were going to get COVID — but I was surprised by how quickly a case was identified.”
Mississippi
The first school district in the state opened last week on Monday in Corinth. A high school student was identified as a case on Friday. Those who had been within six feet of the student for 15 minutes or longer have been notified and are required to quarantine for 14 days and attend classes virtually.
Georgia
More alarming was an outbreak that occurred over three days at an overnight camp in Georgia reported in MMWR this week. A teenage staff member become symptomatic and was tested the following day. When results were available the following day, the campers were sent home.
Campers from other states (27) were not included in the analysis. 597 residents of the state were in attendance. At the time of publication, results were available for 344 (58%), and of those, 260 (76%) were positive. The age range of attendees was 6-19 years old. The authors noted that because a portion of the status of campers was not known, an even higher percentage could be infected, some transmission may have been outside of camp attendance, and it’s unknown how well prevention measures were followed at the camp.
There are a few things worth quoting verbatim from the summary:
“These findings demonstrate that SARS-CoV-2 spread efficiently in a youth-centric overnight setting, resulting in high attack rates among persons in all age groups, despite efforts by camp officials to implement most recommended strategies to prevent transmission. Asymptomatic infection was common and potentially contributed to undetected transmission.”
“Children of all ages are susceptible to SARS-CoV-2 infection and, contrary to early reports, might play an important role in transmission.”
“Physical distancing and consistent and correct use of cloth masks should be emphasized as important strategies for mitigating transmission in congregate settings.”
Teacher Shortages
“Schools across the nation struggle during normal times to find enough substitute teachers to fill classrooms when the assigned teacher calls in sick or must attend a training session. With increased teacher absences expected due to COVID-19, the need for subs is even greater.” The average wage for a substitute teacher is $95/day. It will be interesting to see how many substitutes find the pay worth the risk
Clinical Research in Children
Transmission
Another study was published in JAMA Pediatrics this week had some disturbing findings. In it, they used PCR amplification cycle threshold (CT) values to assess viral load, or in simpler terms, how much virus nucleic acid was present in a sample.
The results are worth noting. “The observed differences in median CT values between young children and adults approximate a 10-fold to 100-fold greater amount of SARS-CoV-2 in the upper respiratory tract of young children. We performed a sensitivity analysis and observed a similar statistical difference between groups when including those with unknown symptom duration. Additionally, we identified only a very weak correlation between symptom duration and CT in the overall cohort “
Essentially that means that among children under five years of age, there was evidence of 10-100x more virus in the upper respiratory tract than those of older children or adults, who had similar values.
They concluded “Thus, young children can potentially be important drivers of SARS-CoV-2 spread in the general population, as has been demonstrated with respiratory syncytial virus, where children with high viral loads are more likely to transmit. Behavioral habits of young children and close quarters in school and day care settings raise concern for SARS-CoV-2 amplification in this population as public health restrictions are eased.”
Disease Characterization
The Lancet published a study on the impact of COVID-19 among 582 children and adolescents in Europe identified by RT-PCR. Parents or siblings were identified as the source of the infection among 60% of them. 75% did not have pre-existing medical conditions. Ten had radiographic findings consistent with acute respiratory distress syndrome (ARDS) and required mechanical ventilation.
One particularly important finding was “individuals with viral co-infection were significantly more likely to require ICU admission, respiratory support, or inotropic support.” That does not bode well for the influenza and RSV season.
Only 93 (16%) never developed clinical symptoms. Four of the children died, two of them had no known pre-existing conditions. “Our data show that severe COVID-19 can occur both in young children and in adolescents, and that a significant proportion of those patients require ICU support, frequently including mechanical ventilation.”
Policy Decisions
An article in NEJM this week takes the position that elementary schools should be reopened. While I agree that the social impacts of closing schools will be harmful on children, there are flaws in their argument.
First, the authors cite relatively low rates of multisystem inflammatory syndrome in children (MIS-C) that was reported in another NEJM article. This study was conducted with data from March 18th until May 20th. The immediate problem in trying to use a rate per 100,000 population is that the pandemic had just been emerging at that time and various lockdown measures had been put in place which have since been eased. During that time period, they identified 186 cases of MIS-C.
The CDC began collecting MIS-C data in mid-May. Between then and July 15th, they have identified 342 cases and 6 deaths of MIS-C, almost double that from the NEJM study. It is also important to remember that in both of these time periods, most schools districts were closed. That is not encouraging for when children are brought together again in a school environment.
Second, they state “Limited emerging evidence suggests that susceptibility to infection also generally increases with age.” and go on so state “Age-related differences in infectivity are less clear. Findings from a few contact-tracing studies suggest that children may be less infectious than adults,” although they do admit that the evidence for the second is weak For both comments, they cite research that has not yet been peer reviewed, which is unusual. The MMWR study about the outbreak at the camp in Georgia clearly provides contrary evidence against those claims.
Third, they make a case that experiences in other countries indicate that opening schools did not seem to have a big impact. The problem in drawing that comparison is that they failed to address the prevalence rate in much of the US, which is alarmingly high in many areas, so that comparison isn’t very useful.
Israel is a good case study.
Israel had taken very aggressive action at the start of the pandemic, and had started their lockdown on March 15th. The Prime Minister Benjamin Netanyahu said “Israel is a success model for many countries” and that “many leaders are calling us to know how to act.”
Schools reopened on May 17th. Israel began to reopen the economy. Beaches, synagogues, and shopping malls opened on May 20th. On May 27th, restaurants, bars, nightclubs, and hotels were allowed to reopen.
Changes that increase or reduce new cases show up three weeks after they are put in place. In the epidemic curve in this graph, the green vertical bar represents three weeks after the lockdown started.
The red bar represents three weeks after schools opened. The yellow bars represent the same interval after the other economic changes were made. It’s clear that all of these three events contributed to the exponential growth that followed.
One item that is particular noteworthy happens two weeks after the impact of schools opening (indicated by dark blue bars). I had previously expected events such as protests, youth sports, and other activities that involved a population composed of individuals who were younger and thus more likely to have milder symptoms or to be asymptomatic to not be indicated in the case data. They would spread the disease to family members and others in their social circles that would be part of the 2nd or 3rd generations of disease from them 2-4 weeks after later if they themselves would have become recognized cases if tested, but didn’t.
As expected, that rise in cases is accompanied by the subsequent rise in deaths a few weeks later.
To the authors’ credit, they did state “The safest way to open schools fully is to reduce or eliminate community transmission while ramping up testing and surveillance. Adults would need to maintain social distance from each other and engage in other measures to reduce adult-to-adult transmission: for example, wearing personal protective equipment (PPE), closing school buildings to all nonstaff adults, and holding digital faculty meetings…If such measures were adopted now, transmission in many states could probably be reduced to safe levels for mid-September or early-October school reopenings.”
Unfortunately, that does not seem to have occurred in many places around the US.
The biggest omission though was a discussion around the long term impacts of infection with COVID-19, which are not known for children.
Long Term Health Impacts
There is more information about the impact of COVID-19 on other organs besides the lungs. What remains unknown is the prevalence of the clinical problems described below in those who have recovered from less severe disease, but it does seem pretty clear that ACE2 receptors are a common link in the pathological mechanism. Even less is known about the pathological findings in children and adolescents from this problems, which could hypothetically cause significant problems later in life.
Cardiac
According to UCSF, a 57-year old woman died of COVID-19. What was very unusual though was while she had mild pneumonia, the virus had ruptured her heart.
“Clinicians, too, were seeing surprising numbers of COVID-19 patients develop heart problems – muscle weakness, inflammation, arrhythmias, even heart attacks…It stands to reason that SARS-CoV-2 affects the heart. After all, heart cells are flush with ACE2 receptors, the virus’s vital port of entry.”
In another study, “A total of 78 patients who recovered from COVID-19 infection (78%) had cardiovascular involvement as detected by standardized CMR, irrespective of preexisting conditions, the severity and overall course of the COVID-19 presentation, the time from the original diagnosis, or the presence of cardiac symptoms.”
Hepatic
Hepatology published a retrospective cohort study of 1826 patients with confirmed COVID-19. “Liver test elevation has been identified as one of a growing spectrum of non-pulmonary manifestations described in COVID-19, which may potentially be attributable to hepatic expression of the primary viral entry receptor, angiotensin converting enzyme II (ACE2). Based on a large systematic review and meta-analysis (17 studies, 2711 patients), liver test abnormalities are estimated to occur in approximately 15% of patients.”
Pulmonary
Lung damage due to the virus has been well documented, both in radiographic and histologic findings. Ackerman et al. found ” severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).”
The commonly repeated trope that COVID-19 is not as deadly than influenza is simply not true.
Vascular
One feature of this disease is the finding of microscopic blood clots in victims during a postmortem examination. Magro et al. reported “In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.” They also proposed a mechanism for this type of injury.
“SARS-Cov1 and SARS-CoV use Angiotensin Converting Enzyme (ACE2) as an entry point to cells. Angiotensin I and angiotensin II have been associated with inflammation, oxidative stress, and fibrosis, and ACE2 is involved in their deactivation. If overwhelming coronavirus infection, with binding to ACE2 on epithelial targets not only in the lung but in other tissues expressing these proteins, including the kidney, intestines, and brain, were to interfere with ACE2 activity, the resulting increases in angiotensin II could lead to reactive oxygen species formation and interference with antioxidant and vasodilatory signals such as NOX2 and eNOS, with further complement activation.
Ackerman et al. also described some of the vascular endothelial implications. “We found greater numbers of ACE2-positive endothelial cells and significant changes in endothelial morphology, a finding consistent with a central role of endothelial cells in the vascular phase of Covid-19. Endothelial cells in the specimens from patients with Covid-19 showed disruption of intercellular junctions, cell swelling, and a loss of contact with the basal membrane. The presence of SARS-CoV-2 virus within the endothelial cells, a finding consistent with other studies, suggests that direct viral effects as well as perivascular inflammation may contribute to the endothelial injury.
It is thought that the damage seen in blood vessels might account for MIS-C, stroke, COVID toe, and other problems.
Behavioral Problems
Essity polled 2,000 British parents about sending their children to school when they are sick. 70% had responded that they had. 60% admitted sending them when knowing that it was contagious. The top five reasons given were:
- Pressure from the school to keep up attendance rates
- Schools are just over-reacting and most the time, children are still OK to go in
- I’m unable to take the time off work
- My child doesn’t want to miss a day of school and have to catch up on school work
- My child didn’t want to miss a day because of a big event such as a play or sports day
Given how many American adults refuse to wear masks, it’s no wonder that a county education department had to create guidelines that state “If your child had a fever overnight or in the morning, please DO NOT give him/her
Tylenol/Motrin and then SEND THEM TO SCHOOL!” It’s unclear how common this practice is, but it could spell problems related to notifying school districts if that data isn’t available and the parent(s) of an infected child decide to send them to school.
Conclusion
Admittedly, there are difficulties and consequences related to moving schools to a completely virtual option. The prevalence of COVID-19 in a community could be helpful in guiding those decisions, but it is imperative to think about the possible long-term impacts of this disease when making these decisions and policies. It’s a high price to pay to solve an immediate problem, especially one where there it is still unclear as to what percentage of transmission indoors is due to droplets versus aerosols, which can stay suspended for long periods of time.
It is odd to hear objections to this based on hunger, abuse, disparity, and socialization from people who have never raised these objections before the pandemic. These problems should be addressed, and should have been addressed long before this problem emerged. There is no greater need to tackle these issues than now given that it will be nearly impossible to keep children, adolescents, teachers, administrators, and support staff safe, as well as their families. It seems to be forgotten that one of the most traumatic things that can happen to a child is the death of a family member.
I don’t claim to have the right answer, but I think I know the wrong one.
