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Augustus de Morgan: “Great fleas have little fleas upon their backs to bite ’em, and little fleas have lesser fleas, and so ad infinitum.”

2020-11-05
WikImage via pixabay.com

Postmortem on COVID-19 patients shows extensive alveolar lung damage and scarring, thromboses, viral RNA in lung cells, and syncytial dysmorphism: Lancet

2020-11-05
sars-cov-2 virions by EM: NIAID

Lancet, on Nov 3, 2020, published an autopsy report with 41 patients who died of COVID-19 pneumonia. This is a highly technical pathology report that describes new findings in virus-infected tissues.

The autopsies showed lungs with thromboses and a few infarctions, viral RNA in pneumocytes and endotheliocytes, and “a large number of dysmorphic pneumocytes, often forming syncytial elements”– besides extensive scarring. Examination of non-lung tissues showed little or no virus infection in most cases.

The presence of thromboses has been widely reported. Scarring and widespread destruction of alveoli were also universally seen. These features have come to be expected in COVID-19. The severe scarring could account for symptoms of persistent shortness of breath in people who appear to have recovered from the infection.

Dysmorphism and syncytia have not been noted, however. The presence of neovascularization and similar signs of new growth was reported previously, but syncytia are a new and troubling finding. This suggests that the reactive process that occurs in virus-infected tissue includes new growth and abnormal cells.

Another troubling finding is the persistence of viral RNA in the lungs, long after the infection has come under attack by the immune system. Continued production of intact virus and shedding into the airways could mean these patients are still contagious even as they have been ill for weeks and are on the point of expiration.

Here is the “findings” section of the abstract:

COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations.

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30480-1/fulltext

In the body of the paper, the authors state that: “They [the findings] support the concept that, different from other forms of interstitial pneumonia and ARDS, the clinical features of COVID-19 patients are not [solely] attributable to extensive DAD, but rather derive from the persistence of infected and dysfunctional cells in the lung.”

In other words, diffuse alveolar damage (DAD) doesn’t explain all the clinical features of COVID-19 pneumonia. Rather, infected, dysfunctional endothelial cells (that form the lung’s inner lining) are causing additional symptoms that account for long-term complications.

The authors say that the dysfunctional cells may explain the development of localized thrombi (blood clots) within the lungs. They blame the syncytial cells on the influence of the “fusogenic S-protein”– that is, the spike protein may cause cells to fuse together.

The paper states that virus-infected or altered cells are largely absent from the rest of the body, despite the findings of studies that showed gastrointestinal (GI) and kidney involvement with at least transient presence of viral RNA in stool and urine.

They propose that the highly inflammatory response that continues in severe infection may be due to the persistence for several weeks of virus-infected, dysfunctional cells in the lungs alone.

The picture that they describe in autopsies suggests that persistence of infection and severe alterations in the lungs, by themselves, can cause the persistence of inflammation and systemic dysfunction through-out the body.

This report is another advance in our understanding of the pathological features of infection with SARS-COV-2 that helps to explain the prolonged nature of the disease in severe cases.

Deborah Birx, MD: a White House coronavirus pandemic response coordinator who doesn’t coordinate

2020-11-03
this is not how to run a pandemic response committee

This post is about Dr. Deborah Birx, who was installed as the White House coronavirus pandemic response team’s coordinator. The team is led by Vice President Mike Pence. There are problems with the team, with Dr. Birx, and with the leader, Mr. Pence. The worst problem, though, is the head of government.

This head has failed to provide over-all leadership and has not taken charge of the federal government’s response. He has effectively turned over responsibility for government response to the state governors, but has failed to provide them with funding or direction. The most prominent result has been a free-for-all among states trying to obtain personal protective equipment (PPE) against the virus: masks, face shields, gowns, gloves, respirators, and the like. Individual states have been forced to compete with the federal government for PPE, frequently being outbid or having their shipments hijacked by federal authorities.

The emphasis of this post will be on the personalities of Dr. Birx and Dr. Redfield. There are so many failures in the federal response that it would take an entire book just to give an overview of them all. I focus this post on Dr. Birx because of an article in Science magazine. This article is titled “The inside story of how [redacted] COVID-19 coordinator undermined the world’s top health agency” and it was published October 14, 2020.

I begin with some direct quotes from the article which describe the effect that Dr. Birx’s personality has had on the CDC. The article starts with a meeting held on July 13, in which a top aide to Dr. Birx announced that the CDC would be relieved of its responsibility for data gathering:

Irum Zaidi, a top aide to White House Coronavirus Task Force Coordinator Deborah Birx, chaired the meeting. Zaidi lifted her mask slightly to be heard and delivered a fait accompli: Birx, who was not present, had pulled the plug on the Centers for Disease Control and Prevention’s (CDC’s) system for collecting hospital data and turned much of the responsibility over to a private contractor, Pittsburgh-based TeleTracking Technologies Inc., a hospital data management company. The reason: CDC had not met Birx’s demand that hospitals report 100% of their COVID-19 data every day.

According to two officials in the meeting, one CDC staffer left and immediately began to sob, saying, “I refuse to do this. I cannot work with people like this. It is so toxic.” That person soon resigned from the pandemic data team, sources say.

Other CDC staffers considered the decision arbitrary and destructive. “Anyone who knows the data supply chain in the U.S. knows [getting all the data daily] is impossible” during a pandemic, says one high-level expert at CDC. And they considered Birx’s imperative unnecessary because staffers with decades of experience could confidently estimate missing numbers from partial data.

“Why are they not listening to us?” a CDC official at the meeting recalls thinking. Several CDC staffers predicted the new data system would fail, with ominous implications. “Birx has been on a monthslong rampage against our data,” one texted to a colleague shortly afterward. “Good f—[uck]ing luck getting the hospitals to clean up their data and update daily.”

When Birx, a physician with a background in HIV/AIDS research, was named coordinator of the task force in February, she was widely praised as a tough, indefatigable manager and a voice of data-driven reason. But some of her actions have undermined the effectiveness of the world’s preeminent public health agency, according to a Science investigation. Interviews with nine current CDC employees, several of them senior agency leaders, and 20 former agency leaders and public health experts—as well as a review of more than 100 official emails, memos, and other documents—suggest Birx’s hospital data takeover fits a pattern in which she opposed CDC guidance, sometimes promoting President [redacted] policies or views against scientific consensus.

https://www.sciencemag.org/news/

This behavior typified Dr. Birx’s management style and caused resentment, reduced morale, and resignations among people working on the pandemic response. Dr. Redfield, as head of CDC, was a weak leader. He was unable to stand up to Dr. Birx. No-one provided overall leadership to compensate for these personality clashes.

In some cases, Dr. Birx promoted the president’s views against those of scientific personnel without logical reasons. Most of these cases were based on opinions expressed by the president at random where he noticed and commented on isolated aspects of the program without focussed attention. In most other cases, the president did not notice or direct the rest of the program and allowed Dr. Birx to do what she thought best without interference.

CDC employees with whom Science spoke—who requested anonymity because they fear retaliation—along with other public health leaders, say Birx’s actions, abetted by a chaotic White House command structure and weak leadership from CDC Director Robert Redfield, have contributed to what amounts to an existential crisis for the agency. And her disrespect for CDC has sent morale plummeting, senior officials say. During a May task force meeting, The Washington Post reported, Birx said: “There is nothing from the CDC that I can trust.”

CDC scientists and others say Birx’s record echoes her approach as head of the President’s Emergency Plan for AIDS Relief (PEPFAR) since 2014. Although that program is widely praised, people who worked on it for years say her draconian management and unrealistic data demands damaged morale and disrupted fieldwork and patient services.

The interviews and documents obtained by Science show Birx replaced a functional, if imperfect, CDC data system—well understood by hospitals and state health departments—with an error-ridden and unreliable filter on hospital needs that sometimes displays nonsensical data, such as negative numbers of beds. Such problems could hamper effective distribution of federal resources during an anticipated fall and winter spike in COVID-19 and flu cases, CDC officials say.

https://www.sciencemag.org/news/2020/10/

There is only one thing I have to add to the analysis by the Science magazine’s reporters: the issue of religious faith. Both Dr. Birx and Dr. Redfield were selected in part because of their staunch Christian religious faith. This selection is a poor basis for making an appointment to a top management position. Both doctors were highly competent within their fields, but both lacked management abilities needed to hold together teams of people with varied backgrounds.

The leader to whom they looked– Vice President Pence– was also highly religious and authoritarian. He followed the instructions of his leader– our current president– without question because of his own authoritarian personality style. The president’s overall leadership was inconsistent and uninformed.

This would not have mattered as much if there had been a well-organized leader at the top who could keep an eye on the ball. Instead, there was a narcissistic, disorganized, uncaring individual who became president almost by accident. He did not have any experience in leading a team of people towards a common goal that transcended the simple management of a real estate company. Worse, he has no concept of learning from experience, so he makes the same mistakes over and over again. We are all suffering the effects of a president who has no concept of organized leadership.

Increased new COVID-19 positive RT-PCR cases set records in US, with hospitals overflowing. Deaths so far have lagged behind due to better treatment. Failure of direction from the top has led to a shambolic response.

2020-11-03
sars-cov-2 virions by EM: NIAID

Today is the end of Election Season, so here is a post about the future that has nothing to do with who wins the election. I haven’t posted about this before because it seemed obvious, but I can’t hold back anymore: records are being set every week now of new COVID-19 positive RT-PCR tests. Hospital cases are following right behind, but deaths so far have not increased as much as before.

One problem not noted in the official new case totals is that, increasingly, cases are being diagnosed by rapid tests. Many of these rapid tests are not being officially recorded, making the record increases even more consequential. Rapid tests are performed onsite or nearby, and they are taking place at urgent care centers and doctor’s offices that are not accustomed to informing the appropriate authorities about positive test results.

The rapid tests are also subject to abuse, in that people without symptoms are being tested– a use not intended by the test makers and likely to be false-negative in cases that have low virus loads. Apparently, asymptomatic individuals can have relatively light infections with fewer viruses being shed– resulting in a lower antigen signal.

The RT-PCR test is supremely sensitive– so much so that it is being accused of being “false-positive” when tiny amounts of virus are detected. The rapid virus tests are not nearly as sensitive, and can miss infections with small virus loads; this is particularly a problem in asymptomatic people. The rapid test is very helpful, but overall direction of the rapid effort should have included full instructions that it’s use should be limited to symptomatic people. This is increasingly evident: a failure of direction from the top has led to sincere but mis-directed efforts to find cases and failure to follow-up with contact tracing.

One example of official failure that I can’t help mentioning is that of a woman who died on an airplane in flight. She was middle-aged, obese, and had asthma; she did not know that she had COVID-19. She experienced increasing respiratory distress in-flight and had an intensive cardiopulmonary resuscitation attempt by a stewardess. The flight was diverted and the dead patient removed, but the diagnosis of COVID-19 was not made until she was autopsied two days later.

Most of the people exposed to her were not informed, and contact tracing was not done. It took three months for all of the people involved to learn of this case. From July 24 until mid-October, when the case was published in the newspaper, no attempts at full notification were performed. This was a failure of federal government agencies, initiated by a lack of overall direction by the administration from the top.

To return to the present: increases in new cases are being followed by increases in hospital admissions, resulting in record numbers of inpatients. These patients are overloading hospitals in places like Denver, Colorado, Salt Lake City, Utah, Boise, Idaho, and Bismarck, North Dakota. Hospitals are talking about transferring patients to places with greater intensive care unit capacity.

By the end of this year, hospitals may have been overloaded, and temporary field hospitals are being set up to handle the overflow. The hospital crush that was seen in New York City in the spring is being seen now in the rural Midwest, West, and Southwest.

The death rates have fallen far behind the new case rates because it now looks like doctors have gotten much better at treating serious cases. Fewer patients are being put on ventilators; more people are getting dexamethasone, which by itself reduces death rates by a third; patients are being turned to prone positions to improve oxygen exchange; and many refinements have resulted in improved survival rates in hospital.

Another problem which has not received enough attention is the plight of people who were not in critical condition during their acute infection but are left with serious after-effects. The rate of “long COVID” has been estimated at 5 to 10% of symptomatic cases. This represents a huge number of people when you take 8 million total positive test results in the last ten months: 400,000 to 800,000 people with persistent symptoms and at least a hundred thousand of them disabled, for a year or possibly permanently. They look like a new generation of myalgic encephalitis/chronic fatigue syndrome.

The virus is coming back in places that were hard hit last spring, but that experienced a remission in the summer: mostly the Northeast.

Places like Connecticut and Massachusetts that had almost eliminated new cases are seeing dramatic increases, doubling the rates from a month ago– although the rates then were so low that even twice as much is not overwhelming.

Everyone is saying that it looks like it is going to be a hard winter. Even Deborah Birx, MD, coordinator of the administration’s shambolic coronavirus task force, was said to have privately issued a warning about the winter. No public confirmation of the warning has been given, presumably because the White House doesn’t want people to know and would rather have rampant rumors spreading around among those who don’t believe the official lies.

Instead, the current president has threatened to “fire” the most trusted scientist working for the government: Anthony Fauci, MD. Dr. Fauci is said to have a 64% approval rating, versus the president’s 36% rating– so an unpopular president would be firing a popular scientist: not a good look. Of course, it is next to impossible for the president to directly fire him because of his Civil Service protections, but he has been eating away at those protections day by day.

No references today: I’m taking a holiday because today is the end of the Election Season. (Besides, it has all been reported by the big newspapers ad nauseam.) Tomorrow comes the real test of democracy: can the people wait for a full count of all the votes, or will they be sucked under by the violent bloviations of a narcissist completely without scruples?

I’m betting that, despite intensive exclamations of “vote rigging”, “fraud”, and “fake news”, the current president will see the winds blowing against him, including expressions of disgust by a few Republicans, and admit defeat (as he has in the past, in the face of intense public outcries.) Then he will make every effort to destroy the government on his way out the door, even pouring glue into the locks before he slams the front door.

CDC: pregnant women have 70% increased risk of dying from COVID-19 versus non-infected pregnant women.

2020-11-03

Morbidity and Mortality Weekly Report (MMWR) published on November 2, 2020, an update on data collected about pregnant women infected with COVID-19, in which they found an adjusted relative risk (aRR) of 1.7, with the raw numbers showing 1.5 vs. 1.2 women per 1,000 cases died during pregnancy. The numbers of deaths are small regardless of infection, which is fortunate; however, there is a significant risk of serious complications and death from COVID-19 even in these young, mostly healthy people.

The report states the following:

 During January 22–October 3, CDC received reports through national COVID-19 case surveillance or through the National Notifiable Diseases Surveillance System (NNDSS) of 1,300,938 women aged 15–44 years with laboratory results indicative of acute infection with SARS-CoV-2. Data on pregnancy status were available for 461,825 (35.5%) women with laboratory-confirmed infection, 409,462 (88.7%) of whom were symptomatic. Among symptomatic women, 23,434 (5.7%) were reported to be pregnant.

After adjusting for age, race/ethnicity, and underlying medical conditions, pregnant women were significantly more likely than were nonpregnant women to be admitted to an intensive care unit (ICU) (10.5 versus 3.9 per 1,000 cases; adjusted risk ratio [aRR] = 3.0; 95% confidence interval [CI] = 2.6–3.4), receive invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2–3.8), receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5–4.0), and die (1.5 versus 1.2 per 1,000 cases; aRR = 1.7; 95% CI = 1.2–2.4).

Stratifying these analyses by age and race/ethnicity highlighted disparities in risk by subgroup. Although the absolute risks for severe outcomes for women were low, pregnant women were at increased risk for severe COVID-19–associated illness.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6944e3.htm

There are other reports that show an increased risk of premature birth, which contradicts previous estimates about which I posted (what seems like ages ago, but must have been less than six months.)

There are other reports today about which I want to post, so I will keep this short: pregnancy, like other “co-morbidities”, confers an increased risk associated with novel coronavirus infections. Pregnant women should be especially careful about isolating themselves, wearing masks when around others, and frequent hand-washing when going to supermarkets and other outside places.

Ideally, pregnant women should not have to go to work and otherwise expose themselves. This is a failing of our “every man for himself” American society that forces everyone to work, regardless of risk factors.

Portable Lung Ultrasound more sensitive, less specific than portable Chest Xray in COVID-19 pneumonia: ACEP presentation

2020-11-01
sars-cov-2 virions by EM: NIAID

A presentation at the American College of Emergency Physicians (ACEP) virtual meeting showed that portable ultrasound examination of the lungs in patients presenting with suspected COVID-19 pneumonia is much more sensitive (although less specific) than portable chest X-ray. If the ultrasound exam is abnormal, a chest CT scan should be performed at once. The presentation was summarized on Medpage Today for November 1, 2020.

From the summary:

In a study of possible COVID-19 patients who presented to the emergency department (ED), ultrasound sensitivity was 97.6% (95% CI 91.6-99.7) versus 69.9% (95% CI 58.8-79.5) for x-ray, reported Ryan C. Gibbons, MD, of the Lewis Katz School of Medicine at Temple University in Philadelphia, in a presentation at the virtual American College of Emergency Physicians meeting.

Gibbons and colleagues prospectively tracked 143 consecutive potential COVID-19 patients who presented at an ED. Each patient was screened via handheld ultrasound and portable x-ray. Those at high-risk, and those who showed abnormal findings, were sent for CT scans.

Physicians interpreted 99 ultrasound scans and 73 x-rays as positive. The CT scans confirmed that 75% (95% CI 66.0-83.2) of these patients had atypical pneumonia. Gibbons said this number is especially high because the patients were tracked during a period of widespread infection.

Specificity was 33.3% (95% CI 16.5-54.0) for ultrasound and 44.4% (95% CI 25.5-64.7) for x-ray.

https://www.medpagetoday.com/meetingcoverage/acep/89433

Based on these findings, the recommended protocol is to proceed directly to CT (computed tomography) scanning when the ultrasound is abnormal. This leads to the best performance and avoids wasting time and energy on portable chest X-rays.

This was, in fact, the procedure followed when the president was hospitalized with COVID-19 in early October. Those not familiar with this technique may have been puzzled by the mention of ultrasounds where past practice would have been a portable chest X-ray. This is one of the innovations that have resulted from experience in the emergency room with the novel coronavirus.

The general public was not advised of the results found when the president was evaluated, and there was no mention of CT scanning. Based on prior behavior with this president, we can assume that the ultrasound was abnormal and that the CT scan confirmed the presence of pneumonia.

The assumption that our current president had COVID pneumonia and was only hospitalized for three days fits with our expectations. We expect that everything about this administration is abnormal and unsafe. A normal president would have spent a week in the hospital under observation and would not have gone for a joy-ride in his hermetically-sealed limousine for the entertainment of his fans.

Regeneron reports results of its “antibody cocktail” treatment for COVID-19: news release

2020-10-30
EM of SARS-COV-2 from Groopman lab

Regeneron has published a news release on October 28, 2020 giving results of its ongoing Phase 2/3 trial of its “antibody cocktail” treatment for COVID-19, showing a greater than ten-fold reduction in viral load and:

“Treatment with REGN-COV2 reduced COVID-19 related medical visits by 72% in patients with one or more risk factor.”

This treatment, called REGN-COV2, is the one touted by our current president after he spent three days in hospital with COVID-19 at the beginning of October. It appears to be highly successful and to have a low incidence of side effects.

From the news release:

Results showed no significant difference in virologic or clinical efficacy between the REGN-COV2 high dose (8 grams) and low dose (2.4 grams). Based on this finding, Regeneron is reviewing potential changes to dosing in the ongoing outpatient clinical trial given the current limited supply of REGN-COV2…

Serious adverse events were numerically more frequent with placebo than REGN-COV2 treatment (0.8% high dose, 1.6% low dose; 2.3% placebo). Numerically more infusion reactions occurred with the REGN-COV2 high dose compared to placebo (1.5% high dose; 0% low dose; 0.4% placebo)…

REGN-COV2 is a combination of two monoclonal antibodies (REGN10933 and REGN10987) and was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19.

To develop REGN-COV2, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. The two potent, virus-neutralizing antibodies that form REGN-COV2 bind non-competitively to the critical receptor binding domain of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Science.

https://investor.regeneron.com/news-releases/news-release-details/regenerons-covid-19-outpatient-trial-prospectively-demonstrates

This monoclonal antibody treatment appears very promising, but unfortunately it is in highly limited supply. Only some 50,000 treatment courses are currently available, less than the daily number of new cases appearing in the US presently. Large quantities of this antibody are unlikely to become available in the future.

Since it is most effective when given early in the course of infection, we are left with the dilemma of choosing to whom it should be given. It is difficult or impossible to predict at the outset which patients will be most affected by the disease, so prioritizing treatment to the sickest will not be possible. Most likely, the treatment will be given to those who can pay the most or who are considered the most valuable to society– not an equitable strategy.

Transmission of SARS-COV-2 Infections in Households: CDC via MMWR, October 30, 2020

2020-10-30
SARS-COV-2 EM photo courtesy NIAID

The Centers for Disease Control (CDC) published a Morbidity and Mortality Weekly Report (MMWR) on October 30, 2020 titled “Transmission of SARS-COV-2 Infections in Households– Tennessee and Wisconsin, April-September 2020.” This report states that 102 of 191 contacts of 101 patients with positive RT-PCR (reverse transcriptase polymerase chain reaction) tests for SARS-COV-2 developed positive RT-PCR tests during follow-up. The secondary infection rate was 53%.

From the report:

For this analysis, 101 households (including 101 index patients and 191 household members) were enrolled and completed ≥7 days of follow-up. The median index patient age was 32 years (range = 4–76 years; interquartile range [IQR] = 24–48 years); 14 (14%) index patients were aged <18 years, including five aged <12 years and nine aged 12–17 years. Among index patients, 75 (74%) were non-Hispanic White, eight (8%) were non-Hispanic persons of other races, and 18 (18%) were Hispanic or Latino (Table 1). Index patients received testing for SARS-CoV-2 a median of 1 day (IQR = 1–2) after illness onset and were enrolled in the study a median of 4 days (IQR = 2–4) after illness onset.

The median number of household members per bedroom was one (IQR = 0.8–1.3). Seventy (69%) index patients reported spending >4 hours in the same room with one or more household members the day before and 40 (40%) the day after illness onset. Similarly, 40 (40%) of index patients reported sleeping in the same room with one or more household members before illness onset and 30 (30%) after illness onset.

Among all household members, 102 had nasal swabs or saliva specimens in which SARS-CoV-2 was detected by RT-PCR during the first 7 days of follow-up, for a secondary infection rate of 53% (95% CI = 46%–60%) (Table 2). Secondary infection rates based only on nasal swab specimens yielded similar results (47%, 95% CI = 40%–54%). Excluding 54 household members who had SARS-CoV-2 detected in specimens taken at enrollment, the secondary infection rate was 35% (95% CI = 28%–43%).

Forty percent (41 of 102) of infected household members reported symptoms at the time SARS-CoV-2 was first detected by RT-PCR. During 7 days of follow-up, 67% (68 of 102) of infected household members reported symptoms, which began a median of 4 days (IQR = 3–5) after the index patient’s illness onset. The rates of symptomatic and asymptomatic laboratory-confirmed SARS-CoV-2 infection among household members was 36% (95% CI = 29%–43%) and 18% (95% CI = 13%–24%), respectively.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6944e1.htm

The report states that, “About 75% of secondary infections were identified within 5 days of the index patient’s illness onset.” As noted in the excerpt above, 54 of the household members were already infected at the time the index patient was enrolled, that is, nearly simultaneously. The report gives recommendations for immediate self-isolation and mask-wearing for all household members. However, that would be too late for those 54 patients.

The data presented in this report are from an ongoing study in two locations: Nashville, Tennessee and Marshfield, Wisconsin. Additional information from this study is likely to be forthcoming.

The study shows that household infections occur commonly and quickly after a member of the household brings home the virus. This makes it imperative for control of this virus that everyone in an affected household be aware of infection status for household members and take appropriate precautions at once.

The CDC is still functioning despite attempts by this administration to undermine and politicize it. This study shows that it is still producing important science and publicizing it to everyone who will listen.

Autoantibodies appear during severe COVID-19 illness: MedRxiv

2020-10-28
EM of SARS-COV-2 from Groopman lab

A preprint (not yet peer-reviewed) article (.pdf full-text version here) appeared on MedRxiv on October 23, 2020 that described the frequent presence of autoantibodies in patients with severe COVID-19 disease.

In these patients, critically ill with COVID-19, more than half showed autoantibodies to a variety of normal constituents of the cell. Some factor that contributes to serious COVID-19 illness also results in the development of autoantibodies.

This has relevance to treatment, explaining why dexamethasone (which suppresses immune reactions) is so effective in severe disease, and suggesting that additional immune suppressive treatments may be helpful.

This also has relevance to explaining why some patients have persistent symptoms long after the viral infection has resolved. Autoantibodies may be causing brain cell damage, damage to both skeletal and heart muscle, and lung problems. Further research will clarify this issue.

Prior to this research, there were findings that anti-interferon antibodies were present in 10% of patients with severe COVID-19 pneumonia. This underscores the importance of interferon in mediating the systemic response to coronavirus infection. (See this article in Science magazine if you dare to learn too much about this.)

The research described in the paper we are talking about today involved 52 patients, almost all of them critically ill with COVID-19 (only two were described as “severe.”) Two-thirds of the patients were male, and 54% of them were African-American (this corresponds to the demographics of serious COVID-19 infections generally– most patients are nonwhite men.)

None of the patients in this study had a prior history of auto-immune disease such as systemic lupus erythematosus or rheumatoid arthritis. Most of the patients had extremely high C-reactive protein (CRP) levels, from 17 to 473 (normal is less than 10; CRP almost always is high– though not this high– in the presence of any infection or inflammation.)

23 of the patients had positive anti-nuclear antibody (ANA) tests, 19 of them with titers of 1:160 or worse (positive ANA is normally found in the setting of lupus erythematosus.) Follow-up testing in seven patients, two weeks later, included four with positive ANA at the outset; one with a titer of 1:80 had resolved at follow-up, but the other three showed 1:360 or worse, one increasing to 1:2560.

Twelve of the patients showed positive rheumatoid factors (RF) (normally seen in rheumatoid arthritis), and ten showed a variety of other autoantibodies (normally seen in other auto-immune diseases.) Some of the patients had both rheumatoid factor and ANA autoantibodies; the number with both is unclear from the figures.

Details of the autoantibodies are shown in Table 1 and Figure 1 of the full-text version of the paper. There are some inconsistencies in the data shown, no doubt due to the fact that the paper has not been reviewed or editorially corrected.

The conclusion of the paper states:

Our findings invite two interpretations. Either patients with undocumented and pre-existing autoimmunity comprise the majority of the critical illness within our Atlanta-based cohort, or more likely, the immunological environment of serious COVID-19 infection, including TLR7 activation by SARS-CoV2 ssRNA [single-stranded ribonucleic acid], is sufficient to drive de novo autoreactivity against a variety of self-antigens.

The latter possibility has been documented in the setting of other serious infections (reference 10: Isenberg, D.A., et al. “Profile of autoantibodies in the serum of patients with tuberculosis, klebsiella and other gram-negative infections” Clin Exp Immunol 67, 516-523 (1987)), and is now mechanistically supported through independent validation of autoimmune-prone EF [extra-follicular] response activation in serious disease (reference 6: Kaneko, N., et al. “Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19” Cell (2020)).

These findings may be consequential for the identification of patients in whom immunomodulation may be beneficial and suggest the value of autoreactivity measurements for proper segmentation and allocation of properly targeted therapies.

They further suggest that simple clinical testing for ANAs or RF may be able to distinguish those groups. Longitudinal study of recovered patients will be critical in understanding the persistence of this autoreactive state, its role in the increasingly documented cases of ‘lingering’ COVID-19 (reference 11: Carfi, A., Bernabei, R., Landi, F. & Gemelli Against, C.-P.-A.C.S.G. “Persistent Symptoms in Patients After Acute COVID-19” JAMA 324, 603-605 (2020)), and its propensity for conversion into self-sustaining autoimmunity– in order to devise early rheumatological intervention strategies and establish effective long-term care protocols.

https://www.medrxiv.org/content/10.1101/2020.10.21.20216192v1.full.pdf

In other words, testing for ANA and RF in serious cases of COVID-19 may identify patients who would benefit from immune-modifying drugs.

More reviews of “What were we thinking”: How 150 books were written about one subject. That’s not including some other important books, named below.

2020-10-27
cartoon courtesy of pixabay.com

The Los Angeles Times published a review of “What Were We Thinking” on October 6: “The meta [redacted] book you didn’t know you needed (and wanted) to read.”

The book’s author states, from the review:

“I imagine that for some people, my book will serve as a ‘He read it so I don’t have to’ rundown of these books,” said Lozada, the Pulitzer Prize-winning nonfiction book critic of the Washington Post, from his home outside Washington, D.C. “Maybe you’ll pick up one or two as a result. That’s great.” But, he adds, “I do hope that there is also a sense of an underlying critique of this moment in American intellectual life.”

https://www.latimes.com/entertainment-arts/books/story/2020-10-06/carlos-lozada-what-were-we-thinking-trump-book-q-a

The Guardian also had a review, on October 10, subtitled, “The Washington Post critic read 150 Trump books, somehow stayed sane and wrote an elegant yet lacerating response.” The reviewer states:

I am both politically liberal and horribly arachnophobic. To liberal readers [redacted] and his presidency resemble footage of a Goliath birdeater. A crawling, creeping horror, an object of terrible fascination, a shifting dark mass from which one cannot tear one’s gaze. Traffic figures to news websites say so. So do publishers’ profits.

https://www.theguardian.com/books/2020/oct/10/what-were-we-thinking-review-carlos-lozada-trump-books

The book is available from Simon and Schuster at their web site. It is also available from Amazon.com, which gives it 4-1/2 stars on 23 reviews and says it’s the number one seller in their “political literature criticism” section.

To be fair, one reviewer mentions that Mr. Lozada left out David Bromwich, American Breakdown: The [redacted] Years and How They Befell Us (London, 2019). The reviewer thinks that is one of the most important books. He states, “Bromwich is a serious omission–one for which there is no excuse, especially since so many of the authors examined aren’t worth the time and trouble.” The reviewer dismisses books by Hugh Hewitt, Michael Wolff, Charles Sykes, and Brian Stelter, among others.

Another reviewer quotes Lozada: ‘One of the ironies of our times is that a man who rarely reads, preferring the rage of cable news and Twitter for hours each day, has propelled an onslaught of book length writing about his presidency’. The reviewer recommends, among Lozada’s 12 most memorable, ‘Know My Name’ by Chanel Miller, and ‘The Fifth Risk’.

Yet another reviewer mentions that Lozada could not include books by  Mary [redacted], Michael Cohen, Peter Strzok, Andrew Weissman, Michael Schmidt, and Bob Woodward, as they were too recent for him to read and still get his book published before the (possible re-) election. This reviewer also mentions the following missing books: Martha Nussbaum (The Monarchy of Fear: A Philosopher Looks at Our Political Crisis) and Adam Gopnik (A Thousand Small Sanities: The Moral Adventure of Liberalism) – plus: Jane Mayer (Dark Money: The Hidden History of the Billionaires Behind the Rise of the Radical Right) and George Packer (The Unwinding: An Inner History of the New America).

The New York Times had a review that came out on the book’s official publication date as well, October 8. From that review:

In 2015, Carlos Lozada, The Washington Post’s Pulitzer Prize-winning book critic, took on a harrowing task: He read eight books “written” by [redacted]. Soon, he expanded the mandate, reading everything he could about [redacted] and the [redacted] era — 150 books in all. It was an act of transcendent masochism, but we should be grateful he did it because “What Were We Thinking” looks past the obvious and perverse — that is, past [redacted] himself — to the troublesome questions raised by the elevation of a soulless carnival barker to the nation’s highest office. 

https://www.nytimes.com/2020/10/06/books/review/what-were-we-thinking-carlos-lozada.html

So many books (and so many reviews of this one book), so little patience. I won’t say I don’t have enough time to read all these books, because actually I do. I just can’t stand the subject material– it’s too enraging to take a chance on. I’d rather read some ancient history.