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Equal amounts of virus in asymptomatic and sick COVID-19 Patients: JAMANETWORK

2020-08-07
EM of SARS-COV-2 from Groopman lab

This study used 303 people who were placed in isolation due to a positive RT-PCR SARS-COV-2 test but few symptoms in South Korea (the Republic of Korea.) Some 36% of them had no symptoms at the time they were isolated; of these 36%, only 19% went on to develop symptoms– meaning about 29% of the people with positive tests never developed symptoms. The study used quantitative testing to discover how much virus each person shed in their nasopharyngeal and lower respiratory secretions (snot and sputum) and found that, on average, people with and without symptoms produced the same amounts of virus. This suggests that asymptomatic people are equally likely to be infectious to others and should be isolated as well (which we would be doing, if we got the test results in time.)

Here’s the findings and discussion from the abstract:

Findings  In this cohort study that included 303 patients with SARS-CoV-2 infection isolated in a community treatment center in the Republic of Korea, 110 (36.3%) were asymptomatic at the time of isolation and 21 of these (19.1%) developed symptoms during isolation. The cycle threshold values of reverse transcription–polymerase chain reaction for SARS-CoV-2 in asymptomatic patients were similar to those in symptomatic patients.

Meaning  Many individuals with SARS-CoV-2 infection remained asymptomatic for a prolonged period, and viral load was similar to that in symptomatic patients; therefore, isolation of infected persons should be performed regardless of symptoms.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2769235

These people were relatively young (median age, 25) and two-thirds were women. It took about six days on average to get a person into the quarantine dormitory after making a diagnosis; the location was specially selected to hold those with few or no symptoms. For this reason, the virus amounts described are not typical for patients with severe symptoms.

The symptoms consisted mainly of cough and runny nose (about half of patients for each) with sputum in 28%, followed by sore throat (a quarter), loss of smell, upset stomach, and diarrhea (less than 10% each.) Only one patient was transferred to hospital– for severe vomiting.

On average, those who didn’t develop symptoms at first took 15 days to become symptomatic. One-third of asymptomatic people cleared in two weeks, and three-quarters cleared after three weeks. Patients who had symptoms or developed them cleared in about 30% of cases after two weeks and 70% after three weeks.

The median time to clearing was 17 days in asymptomatic people and 19.5 days in symptomatic (including presymptomatic) patients. It’s important to note that a positive test doesn’t equate to shedding of infectious virus. The study looked at three parts of the virus genome and found that not all parts were detectable in low-positive tests, suggesting that the virus genome was broken up in those cases.

The study suggests that people without symptoms are probably equally likely to transmit infection when they expose others as are patients with symptoms. The authors recommend that asymptomatic people should be isolated too in order to prevent spread of the infection.

The duration of quarantine that best prevents spread is unknown– initially two weeks from onset of symptoms was recommended, but recently that has been reduced to ten days. For someone with no symptoms, there is no clear time, although it’s probably less than for sick people. There is no clear division, and positive tests with highly sensitive assays like the RT-PCR don’t mean someone is still infectious.

Unfortunately, a news story from Santa Clara County, California says that test results are taking as long as 16 days to be returned– rendering them useless from an infection control point of view. We don’t have any way to control the spread of infection by isolating people in this country unless we dramatically improve testing capacity and turnaround time.

The drastic isolation measures that were taken in South Korea are impossible here, in part because so many people are testing positive now, and in part because it takes so long to get the results. A strategy of rapidly producing tests, especially those that give immediate results, would have been a big help. It’s too late now.

It appears that a vaccine, rapidly produced and rapidly administered to everyone, is the only hope to control the spread of COVID-19 in this country. Will there be a national will to accept a vaccine? I don’t think so. Too many people are too selfish and unscientific.

Seismic Noise Has Dropped by up to 50%, allowing quieter earthquakes to be detected. That’s me you hear yelling.

2020-04-09

1029181244

a photo of me, by me, looking quizzical. I’m not mad, really I’m not. Or we’re all mad here.

This morning I posted a link to a NYT story that had multiple bits of new information.  One of the more important bits (that I didn’t get to this morning) was that seismometers all over the world have responded to the lockdown orders that have some 90% of the world’s population staying home other than for essential activities.  I personally was little affected by that order (even though I live in California).

As a result of that “stay at home” order, we (not I) are mostly staying at home.  I still take walks in the splendid isolation of my abode among the peach and almond trees.  I still go to the pharmacy for the medications that I take, most important of which is ibuprofen.  I still go to the grocery store.  All my banking needs are taken care of online and most of my bills are paid online.

My wife is still working as a physician assistant.  We still fill up the gas tank on our Toyota Highlander.  Nothing has changed except that I am posting to this blog more frequently.

Yet the seismometers say the world is quieter, and as a result we can hear the smaller earthquakes and the little things that are just the earth’s crust moving around.  What is more, the air quality in Los Angeles has greatly improved.  Now wouldn’t it be grand if all of the people who were running around like chickens with their heads cut off would just stay still?

I know, that’s terribly cynical.  I do feel bad, very bad, for all the people who are dying miserably, alone, because they are under quarantine or isolation in the hospital.  Yet human existence is suffering, or so the Buddha says.

So, if you meet the Buddha on the road, kill him.  Or don’t.  I’d rather you didn’t.  You don’t have to follow every ridiculous instruction you get, do you?

Only follow an instruction if it makes sense– or if you can make sense out of it, which means you may have to think about it for a while.

What did the Buddha mean when he said, if you meet the Buddha on the road, kill him?  Let me know if you figure out what it means.  I’ll be sitting here, quietly listening.

Reports of COVID-19 outbreaks at meatpacking plants: MMWR

2020-08-07
EM of SARS-COV-2 from Groopman lab

Two reports of COVID-19 outbreaks at meatpacking plants in South Dakota and Nebraska were published in Morbidity and Mortality Weekly Report (MMWR) by the Centers for Disease Control. The reports show that this virus spreads rapidly in the crowded, low temperature environments of meat processing facilities.

This report of the South Dakota outbreak was dated August 7 and said:

During March 16–April 25, 25.6% (929) of employees at a meat processing facility in South Dakota and 8.7% (210) of their [outside] contacts were diagnosed with COVID-19; two employees died. The highest attack rates occurred among employees who worked <6 feet (2 meters) from one another on the production line.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6931a2.htm?s_cid=mm6931a2_x

The second report, also dated August 7, described a testing program set up by the Nebraska Department of Health and Human Services and run in cooperation with a meatpacking plant. Tests were offered to all workers at the plant, although it is unclear how many total workers there were there. The report begins:

Among 1,216 Nebraska-resident meat processing facility workers tested, 375 (31%) had positive results. During May 8–25, case investigators attempted to interview the 349 workers who had positive test results and available phone numbers; five refused, 99 were not reached after five attempts, and four did not report symptom status, leaving 241 (69%) of the attempted interviews for analysis.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6931a3.htm?s_cid=mm6931a3_x

Of the positive-tested workers who were available to interview, a third reported no symptoms. Most of them were exposed at work, although only 29% reported close contact with someone visibly ill or diagnosed with infection. 13% reported contact with someone outside of work. Two of those with symptoms were hospitalized, and none died.

These two reports from MMWR are limited and inadequate, but they do show that meat processing plants are an ideal place to transmit infection with SARS-COV-2. The low temperatures and crowding probably explain the high transmission rates seen at these plants. Other meat processing facilities have had similar outbreaks, although there is less publicity.

This article from a Lincoln, Nebraska paper dated June 4 says: “More than 3,000 workers at Nebraska meatpacking and meat processing facilities have tested positive for COVID-19, and nearly every plant of any size in the state has had a significant outbreak.” With the exception of one plant run by Cargill in Nebraska City, which acted early to prevent infections.

If there were better separation between workers and more use of masks, this might reduce transmission rates– as was seen at some Cargill plants, according to the newspaper account. Some of the recommendations have been implemented at other plants since the outbreaks occurred.

These reports illustrate two features of the pandemic in this country: poor people who can’t afford to stop working and isolate themselves are most likely to be infected; and those in power will do as little as possible to help them– except for an enlightened few.

For instance, there’s this from Greg Sargent in the Washington Post:

The crisis has also revealed that minority workers are overrepresented in “essential” jobs, putting them at much greater risk, yet often without safety precautions or just compensation. The heavily concentrated meatpacking industry has been been characterized by horrifyingly substandard and lethal conditions.

https://www.washingtonpost.com/opinions/2020/08/07/trump-fiasco-just-got-worse-that-gives-biden-hidden-opening/

Questions about SARS-COV-2 and gastrointestinal COVID-19

2020-08-06
SARS-COV-2 EM photo courtesy NIAID

A patient who was admitted for treatment of rectal adenocarcinoma had specimens taken from the rectum during the performance of an ileostomy (the cancer was cut out and his bowel was given a new outlet to the skin.) Three days later he developed symptoms and was diagnosed with COVID-19 that progressed to pneumonia. The samples taken at surgery showed replicating (growing) SARS-COV-2 virions (individual virus particles) in the tissue under the electron microscope (EM.)

The only conclusion you could make from that is that he was shedding virus in his stool three days before he developed symptoms of COVID-19.

This is a typical phenomenon. A case series of 42 patients with confirmed COVID-19 had the virus isolated from the stool of 28 of them, which persisted for an average of a week after it was no longer detectable in the nose.

A large meta-analysis early in the outbreak found 48% of 4243 patients with positive tests for virus RNA in stools, but only 18% had symptoms. Again, virus RNA was detected in stool after it had disappeared from respiratory samples.

Another study, with 95 patients, found that if anorexia and nausea are included as gastrointestinal (GI) symptoms, 58 of the patients (more than half) did in fact have GI problems. 31 of 65 patients whose stool was tested were positive for virus RNA.

This study, which included 116 consecutive patients, identified liver enzyme increases in 40% of the 65 patients tested for liver function. There were 32% of all patients who complained of GI symptoms, but they were mild compared to the cough and dyspnea. The authors also remarked that GI symptoms were never the first sign of illness.

These studies make it clear that SARS-COV-2 frequently, if not always, infects the GI tract, but doesn’t always cause diarrhea. These symptoms are relatively mild– unlike those in the blood vessels, lungs, and heart. The virus even affects skin: this report from the United Kingdom says that 8-9% of patients complained of rashes.

The virus invades the lung and causes pneumonia in a large proportion of patients with symptoms. It also affects the heart in most patients, if the studies of post-viral heart MRI scans are accepted. It seems to be the case that the virus can invade every part of the body because it affects blood vessel endothelium (lining) and there is no organ other than the cornea free of blood vessels.

Ohio’s governor Mike DeWine tests positive for SARS-COV-2 before meeting He-who-must-not-be-named. Good excuse.

2020-08-06
official-type photo of Mike DeWine

Just before meeting the president, everybody has to be tested for the virus, because He is a professed “germaphobe” and the tests are available (although there seems to be a problem with a high false-negative rate.) There’s no indication that He understands the concept of false-negative and false-positive, which is not surprising since a lot of doctors don’t understand it either.

Here’s an article in the Washington Post about it. Here’s another story in CNN. It’s unfortunate for him, especially because he aggressively responded to the threat of the novel coronavirus when it first was manifested. It is fortunate for him that he is asymptomatic. I hope it’s not a false-positive, because he could be quarantining for nothing. I also hope he gets tested for antibodies after he comes out of quarantine.

I wish only the best for people suffering from the virus. I don’t have such gentle feelings for a certain president. I hope He experiences justice, in the form of the long arm of the law. In that regard, you do know that He’s under investigation by the New York State Attorney General in Manhattan?

For bank, insurance, and possibly tax fraud (CNN story) going back over many years. It seems that His former lawyer testified under oath that He had a habit of inflating and deflating the values of his properties on applications, depending on which favored His interests more.

Just letting you know how I feel about these things. I don’t like the fact that we are experiencing the worst outbreak of the virus in the developed world. I don’t like the fact that poor people and people of color are experiencing the worst effects, both virological and economical. I don’t like the way this has been politicized. I do like the effects of it upon His chances for re-election.

Diffusion Tensor Imaging– what is it? New form of MRI scanning that is as yet poorly defined

2020-08-06
mri image by kalhh courtesy of pixabay.com

Read this article, “An introduction to diffusion tensor image analysis”, to get an idea of just what “diffusion tensor imaging” is, but be prepared for abstruseness. Yesterday I posted about the brain effects of COVID-19, and a paper came up that talked about changes on DTI. Unfortunately, the changes are ill-defined and the field of DTI is new and not well established.

I cited this article but reading it didn’t really clarify just what DTI is– it only made it clear that the changes one finds don’t correspond to clear pathological changes in the brain. The technique works well in squid axons, but that’s not what we’re interested in right now.

So, just to clarify, it’s just not clear.

High attack rate of COVID-19 on Diamond Princess supports aerosol transmission: MedRxiv

2020-08-05
em coronavirus from NIAID– CC license

This new post on MedRxiv dated July 13 and posted July 15 uses a mathematical model to estimate the chances of the attack rate being caused by fomite transmission, droplets, or aerosols– and decides that aerosol transmission of the SARS-COV-2 virus contributes significantly to infection and disease with COVID-19.

To recap: the cruise ship Diamond Princess embarked on January 20, 2020 with a single (later identified) case of COVID-19. By the time the ship was emptied (after a quarantine that ended February 18), of  “3,711 passengers and crew on board, there were 621 (17%) symptomatic and asymptomatic people with positive COVID-19 tests. ” (Center for Evidence-Based Medicine, https://www.cebm.net/study/covid-19-transmission-of-the-novel-coronavirus-onboard-the-diamond-princess-cruises-ship/)

Apparently, not all of the people on board were tested, but at least 3,000 were checked at some point. It is fairly clear from other information available that the 17% positive rate is an undercount. At least 18% were completely asymptomatic and possibly many more. (https://pubmed.ncbi.nlm.nih.gov/32183930/)

Another study gives 696 people infected by February 25 and 7 deaths by March 2. (9 more cases identified by March 5 are given as “negative cases.”) This study also points out that the passengers tended to be older; it seems that none were children. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118348/)

From the abstract of the new study:

 The current prevailing position is that coronavirus disease 2019 (COVID-19) is transmitted primarily through large respiratory droplets within close proximity (i.e., 1-2 m) of infected individuals. However, quantitative information on the relative importance of specific transmission pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., droplets, aerosols, and fomites across short- and long-range distances) remains limited….

We developed a framework that combines stochastic Markov chain and negative exponential dose-response modeling with available empirical data on mechanisms of SARS-CoV-2 dynamics and human behaviors, which informs a modified version of the Reed-Frost epidemic model to predict daily and cumulative daily case counts on the ship…..

 Mean estimates of the contributions of short-range, long-range, and fomite transmission modes to infected cases aboard the ship across the entire simulation time period were 35%, 35%, and 30%, respectively. Mean estimates of the contributions of large respiratory droplets and small respiratory aerosols were 41% and 59%. Short-range transmission was the dominant mode after passenger quarantine began, albeit due primarily to aerosol transmission, not droplets. Interpretation Our results demonstrate that aerosol inhalation was likely the dominant contributor to COVID-19 transmission among passengers aboard the Diamond Princess Cruise Ship…..

these findings underscore the importance of implementing public health measures that target the control of inhalation of aerosols in addition to ongoing measures targeting control of large droplet and fomite transmission, not only aboard cruise ships but in other indoor environments as well.

https://www.medrxiv.org/content/10.1101/2020.07.13.20153049v1

When we say “aerosol” transmission we are talking about tiny droplets, less than 10 microns in diameter (the virus itself is 50-200 nanometers, or 0.05-0.2 microns) and these aerosols can float on air currents for long periods of time, from a few minutes to an hour or so. The chances of a 10 micron drop containing a virus are not individually great, but with thousands of these drops being emitted every second during breathing and talking, there is a good chance that some will contain infectious material. Epithelial cells from a person’s airway will have many viruses attached to them.

These aerosols can land anywhere on a targeted person and be breathed into the lungs or deposited on the eyes (I’m just saying that to sound scarier.) The point is that exposure to aerosols is scary.

The spread of droplets and aerosols can be reduced by masks (I have posted about this before on several occasions; see May 15 on droplet size for example.) So, do wear that mask.

SARS-COV-2, COVID-19, and the brain

2020-08-04
SARS-COV-2 particles emerging from a dying cell: EM by NIAID

The novel coronavirus can invade the brain and has shown up in the cerebrospinal fluid. There is now evidence that many patients who appear to have recovered from COVID-19 have subtle alterations in their brains, which may be due to low-grade viral invasion.

The significance of these findings is primarily in that it may explain why so many people who think they have recovered are still having problems with fatigue/lassitude (that is, not on exertion like from a weak heart), loss of memory, and even depression.

Previous MRI (magnetic resonance imaging) studies have focussed on patients with severe, acute illness who have signs of stroke or brain hemorrhage, or else various neurological disorders suggesting encephalitis (or other major problems.)

Scroll down to the last study excerpted in this post for the “subtle brain alterations”– be prepared for “diffusion tensor imaging”– which will be explained in this article.

This study, which was just published in Lancet yesterday, August 3, uses diffusion tensor imaging to show that there are alterations in several brain regions which don’t rise to the level of dead tissue or blood clots, but still might mean that there is significant damage. I saved it for last because the other studies show the more serious things that can happen in severe illness.

Strokes and hemorrhages

Here is an MRI examination of 37 patients with severe COVID-19: half of them had hemorrhage (“stroke”). From the Results:

Thirty men (81%) and 7 women (19%) met inclusion criteria, with a mean age of 61+/- 12 years (range: 8-78). The most common neurologic manifestations were alteration of consciousness (27/37, 73%), pathological wakefulness when the sedation was stopped (15/37, 41%), confusion (12/37, 32%), and agitation (7/37, 19%). The most frequent MRI findings were: signal abnormalities located in the medial temporal lobe in 16/37 (43%, 95% CI 27-59%) patients, non-confluent multifocal white matter hyperintense lesions on FLAIR and diffusion sequences, with variable enhancement, with associated hemorrhagic lesions in 11/37 patients (30%, 95% CI 15-45%), and extensive and isolated white matter microhemorrhages in 9/37 patients (24%, 95% CI 10-38%). A majority of patients (20/37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation: higher admission rate in intensive care units, 20/20 patients, 100% versus 12/17 patients, 71%, p=0.01; development of the acute respiratory distress syndrome in 20/20 patients, 100% versus 11/17 patients, 65%, p=0.005. Only one patient was positive for SARS-CoV-2 RNA in the cerebrospinal fluid.

https://doi.org/10.1148/radiol.2020202222

Another study of 27 patients with neurological problems; Results:

Brain MRI was performed in 27/50 (54%) patients with neurologic symptoms (Fig 1). The median age of patients with MRI was 63 years (range 34-87 years, 21 males) (Table). 12/27 (44%, 95%CI 25-65%) patients who had MRI had acute findings. In 10/27 (37%) patients, cortical FLAIR signal abnormality (Fig 2; Appendix E1, Figs E1-E4) was present. Accompanying subcortical and deep white matter signal abnormality on FLAIR images were each present in 3 patients. Abnormalities involved the frontal lobe in 4, parietal lobe in 3, occipital lobe in 4, temporal lobe in 1, insular cortex in 3 and cingulate gyrus in 3 patients.

Cerobrospinal fluid (CSF) was obtained in 5 out of 10 patients with cortical signal abnormalities. Total protein was elevated (mean 79.9 mg/dL, range 59.9 – 109.7 mg/dL) in 4 of these patients. The cell count, glucose levels, IgG index, albumin were within normal limits, and RT-PCR for HSV DNA and SARS-CoV-2 were negative in all 5 specimens. Oligoclonal bands were checked in 3 specimens and were negative.

Other acute intracranial findings in the absence of cortical signal abnormality included 1 patient with acute transverse sinus thrombosis and 1 patient with acute infarction in right middle cerebral artery territory.

In 15/27 cases (56%), MR did not reveal any COVID-19 related or acute intracranial findings. CSF was obtained in two of these cases which showed elevated CSF protein (mean 98 mg/dL) despite negative MRI. A full description of MRI findings is in the supplement at the end of this article (Appendix E1).

https://pubs.rsna.org/doi/10.1148/radiol.2020201697

From an autopsy study, the Results:

Among the 62 patients who died from COVID-19 from 31/03/2020 to 24/04/2020 at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed.

https://n.neurology.org/content/early/2020/06/16/WNL.0000000000010116

Loss of smell (anosmia)

A single 25 y/o patient with anosmia had this:

A 25-year-old female radiographer with no significant medical history who had been working in a COVID-19 ward presented with a mild dry cough that lasted for 1 day, followed by persistent severe anosmia and dysgeusia. She did not have a fever. She had no trauma, seizure, or hypoglycemic event. Three days later, nasal fibroscopic evaluation results were unremarkable, and noncontrast chest and maxillofacial computed tomography results were negative. On the same day, a brain MRI was also performed. On 3-dimensional and 2-dimensional fluid-attenuated inversion recovery images, a cortical hyperintensity was evident in the right gyrus rectus (Figure 1) and a subtle hyperintensity was present in the olfactory bulbs (Figure 1). Because many patients in Italy are experiencing anosmia  (https://academic.oup.com/cid/article/71/15/889/5811989) and the cortical signal alteration was suggestive of viral infection, a swab test was performed and reverse transcription–polymerase chain reaction analysis yielded positive results for SARS-CoV-2. During a follow-up MRI performed 28 days later, the signal alteration in the cortex completely disappeared and the olfactory bulbs were thinner and slightly less hyperintense (Figure 24). The patient recovered from anosmia. No brain abnormalities were seen in 2 other patients with COVID-19 presenting anosmia who underwent brain MRI 12 and 25 days from symptom onset.

https://jamanetwork.com/journals/jamaneurology/fullarticle/2766765

But then a larger study showed “nonspecific white matter angiopathy”:

 Two hundred forty-two patients with COVID-19 underwent CT or MRI of the brain within 2 weeks after the positive result of viral testing (mean age, 68.7 ± 16.5 years; 150 men/92 women [62.0%/38.0%]). The 3 most common indications for imaging were altered mental status (42.1%), syncope/fall (32.6%), and focal neurologic deficit (12.4%). The most common imaging findings were nonspecific white matter microangiopathy (134/55.4%), chronic infarct (47/19.4%), acute or subacute ischemic infarct (13/5.4%), and acute hemorrhage (11/4.5%). No patients imaged for altered mental status demonstrated acute ischemic infarct or acute hemorrhage. White matter microangiopathy was associated with higher 2-week mortality (P < .001). Our data suggest that in the absence of a focal neurologic deficit, brain imaging in patients with early COVID-19 with altered mental status may not be revealing.

 http://www.ajnr.org/content/41/7/1179

Diffusion Tensor Imaging

Finally, a study using diffusion tensor imaging in MRI scans showed numerous subtle alterations during the recovery phase. This from the Findings and Interpretation:

In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl’s gyrus and right cingulate gyrus and a general decline of MD [mean diffusivity], AD [axial diffusivity], RD [radial diffusivity] accompanied with an increase of FA [fractional anisotropy] in white matter, especially AD in the right CR [corona radiata], EC [external capsule] and SFF [superior fronto-occipital fasciculus], and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV [gray matter volume], GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl’s gyrus, and Global MD of WM [white matter] were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH [lactate dehydrogenase] level (p value <0.05).

Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30228-5/fulltext

Comment of the Day: “damnatio memoriae” should be revived.

2020-08-04
photo courtesy of pixabay.com and Erika Wittlieb

This from phimac in Washington Post attached to an op-ed by George Conway:

Classical Rome had “damnatio memoriae”: Forbidding the offender’s name to be spoken, cancelling it in every document and removing it from any memorial. A custom to be revived, methinks.

https://www.washingtonpost.com/opinions/2020/08/03/trumps-name-should-live-infamy/

A child is the index case in 10% of household infections with SARS-COV-2, not statistically significant: MedRxiv and others

2020-08-04
EM SARS-COV-2 emerging from apoptotic cells: NIAID

An opinion article in “Medpage Today” on August 3 makes the argument that “it depends” on local infection rates, school mitigation measures, and individual student characteristics as to whether it’s possible to safely open schools for in-person instruction. Let’s look at the research cited in the opinion piece as data supporting some of their arguments.

This paper in MedRxiv was cited as showing that children were the index case in only 10% (3/31) cases of household transmission. That number– 31 cases of household transmission– is too small to help us draw a picture of the tendency of children to pass the novel coronavirus on to members of their households or to their teachers and staff at school. Here are the results from the abstract:

Of the 31 household transmission clusters that were identified, 9.7% (3/31) were identified as having a paediatric index case. This is in contrast other zoonotic infections (namely H5N1 influenza virus) where 54% (30/56) of transmission clusters identified children as the index case.

https://www.medrxiv.org/content/10.1101/2020.03.26.20044826v1

The article states that they considered the possibility that asymptomatic children were index cases and reported that only 19% of the children were asymptomatic. Other studies show a much larger proportion of asymptomatic cases, even in adults. This leaves open the possibility that asymptomatic children were index cases, who had time to become antigen-negative before cases in the rest of the family were identified.

The other possibility is that adults were more likely to be index cases because children had not yet been exposed through school or their playmates. This would be impossible to evaluate given the nature of the epidemic at that stage.

This is not helpful: a statement by the president on July 30 that “Young people are almost immune to this disease.” As usual, he spreads misinformation, disinformation, and in this case, scientifically inaccurate statements, to further his arguments.

Then there is this article in Nature, which makes this statement in the abstract:

We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12–31%) of infections in 10- to 19-year-olds, rising to 69% (57–82%) of infections in people aged over 70 years. 

https://www.nature.com/articles/s41591-020-0962-9

The paper uses this information (which is suspect) to make this conclusion: “…interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low.” We have no idea how transmissible subclinical infections are. If “interventions aimed at children” refers to keeping schools closed, remember that teachers and staff are adults, and they are the ones most at risk. If they catch an infection from an asymptomatic child, the consequences are equally severe, and we don’t know how contagious that child without symptoms may be.

There is much, much more to be considered. For example, did you know that children can excrete the virus in their stool for long periods of time after they have recovered and show no virus in the nose?

This study from China looked at the three children they had whose stools were tested. Two of them had virus in the stool three weeks after they had apparently recovered.

Prolonged shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

https://www.medrxiv.org/content/10.1101/2020.03.11.20033159v1

Then there is this, from a case series of ten children with COVID-19:

Surprisingly, we also noted a high frequency (83.3% [5 of 6 tested]) of 2019-nCoV RNA detection in feces in mild patients and prolonged virus
RNA shedding in feces for at least 2 weeks and even more than 1 month, which raises a question concerning whether the gastrointestinal tract may be another site of viral replication. The impact on 2019-nCoV shedding in feces on transmission model and infection prevention and control should be further assessed.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108143/pdf/ciaa198.pdf

From these studies, we can see that children often have prolonged shedding of virus in stool. This is a problem for transmission, especially in smaller children who have less ability to separate oral from fecal, uh, tactile exploration, shall we say, delicately. Another area where not enough is known to be confident about school attendance.

This report came from MMWR (part of CDC) online April 6:

Data on signs and symptoms of COVID-19 were available for 291 of 2,572 (11%) pediatric cases and 10,944 of 113,985 (9.6%) cases among adults aged 18–64 years (Table). Whereas fever (subjective or documented), cough, and shortness of breath were commonly reported among adult patients aged 18–64 years (93% reported at least one of these), these signs and symptoms were less frequently reported among pediatric patients (73%). Among those with known information on each symptom, 56% of pediatric patients reported fever, 54% reported cough, and 13% reported shortness of breath, compared with 71%, 80%, and 43%, respectively, reporting these signs and symptoms among patients aged 18–64 years. Myalgia, sore throat, headache, and diarrhea were also less commonly reported by pediatric patients. Fifty-three (68%) of the 78 pediatric cases reported not to have fever, cough, or shortness of breath had no symptoms reported, but could not be classified as asymptomatic because of incomplete symptom information. One (1.3%) additional pediatric patient with a positive test result for SARS-CoV-2 was reported to be asymptomatic.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm

Roughly ten percent of cases of COVID-19 had information on signs and symptoms. Likewise, later in the report it states that roughly 30% of the cases had information on whether the patients were hospitalized. This shows the deep inadequacy of the reporting mechanisms, starting early in the pandemic; at that stage, there were 239,279 cases and 5,443 deaths in the US, already a quarter of the world’s cases although only 1/9 of the world’s deaths.

The bottom line is that we have failed as a country. We didn’t even collect vitally important information about the cases we had in the beginning. Our federal government’s response to this pandemic should have been the best in the world; instead, it is below that of almost all other developed nations and on a par with poor countries like Brazil.

Under these circumstances, returning to school for in-person instruction is worse than foolhardy– it is criminal.

Comment of the Day

2020-08-04

This from phimac in Washington Post attached to an op-ed by George Conway:

Classical Rome had “damnatio memoriae”: Forbidding the offender’s name to be spoken, cancelling it in every document and removing it from any memorial. A custom to be revived, methinks.

https://www.washingtonpost.com/opinions/2020/08/03/trumps-name-should-live-infamy/