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Some Cheery COVID Research Tidbits

16 Thursday Jul 2020

Posted by pnoetx in Pandemic, Public Health, Uncategorized

≈ 1 Comment

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ACE Inhibitors, Angiotensin Drugs, ARBs, bacillus Calmette-Guerin, BCG Vaccine, Blood Plasma, Cholesterol, Coronavirus, Covid-19, Derek Lowe, Gilead Sciences, Herd Immunity, Hydroxychloroquine, Immune Globulin, Instapundit, Lancet, Marginal Revolution, National Academies of Science Engineering and Medicine, Off-Label Drugs, Oxford, R0, Remdesivir, SARS-CoV-2, Severe Acute Respiratory Syndrome, Statins, T-Cell Immunity, Transmissability, Tricor, Tuberculosis, Viral Load

Here’s a short list of new or newish research developments, some related to the quest to find COVID treatments. Most of it is good news; some of it is very exciting!

Long-lasting T-cell immunity: this paper in Nature shows that prior exposure to coronaviruses like severe acute respiratory syndrome (SARS) and even the common cold prompt an immune reaction via so-called T-cells that have long memories and are reactive to certain proteins in COVID-19 (SARS-CoV-2). The T-cells were detected in both C19-infected and uninfected patients. This comes after discouraging reports that anti-body responses to C19 are short-lived, but T-cells are a different form of acquired immunity. Derek Lowe says the following:

“This makes one think, as many have been wondering, that T-cell driven immunity is perhaps the way to reconcile the apparent paradox between (1) antibody responses that seem to be dropping week by week in convalescent patients but (2) few (if any) reliable reports of actual re-infection. That would be good news indeed.”

The herd immunity threshold (HIT) is much lower than you think: I’ve written about the effect of heterogeneity on the HIT before, here and here. This new paper, by three Oxford zoologists, shows that the existence of a cohort having some form of prior immunity, innate or acquired, reduces the number of infections required to achieve the HIT. For example, if initial transmissibility (R0) is 2.5 and 40% of the population has prior immunity (both reasonable assumptions for many areas), the HIT is as low as 20%, according to the authors’ calculations. That’s when the contagion begins to recede, though the final infected share of the population would be higher. This might explain why new cases and deaths have already plunged in places like Italy, Sweden, and New York, and why protests in NYC did not lead to a new wave of infections, while those in the south appear to have done so.

Seasonal effects: viral loads might be decreasing. From the abstract:

“Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation. Mucosal barrier and mucociliary clearance can significantly decrease viral load and disease progression, and their inactivation by low relative humidity of indoor air might significantly contribute to severity of the disease.”

The BCG vaccine appears to be protective: this is the bacillus Calmette-Guérin tuberculosis vaccine administered in some countries, This finding is not based on clinical trials, so more work is needed.

Is there no margin in plasma? No subsidy? This is the only “bad news” item on my list. It’s widely agreed that blood plasma from recovered C19 patients can be incorporated into an immune globulin drug to inoculate people against the virus. It’s proven safe, but for various reasons no one seems interested. Not the government. Not private companies. Did Trump happen to mention it or something?

C19 doesn’t spread in schools: this German study demonstrates that there is little risk in reopening schools. One of the researchers says:

“Children act more as a brake on infection. Not every infection that reaches them is passed on…. This means that the degree of immunization in the group of study participants is well below 1 per cent and much lower then we expected. This suggests schools have not developed into hotspots.”

Also worth emphasis is that remote learning leaves much to be desired, as acknowledged by the National Academies of Science, Engineering and Medicine, which has recommended that schools reopen for younger children and those with special needs.

Can angiotensin drugs (ACE Inhibitors/ARBs) reduce mortality? This meta-analysis of nine studies finds that these drugs reduce C19 mortality among patients with hypertension. The drugs were also associated with a reduction in severity but not with statistical significance. These results run contrary to initial suspicions, because ACEI/ARB drugs actually “up-regulate” ACE-2 receptors, to which C19 binds. Researchers say the drugs might be working through some other protective channel. This is not a treatment per se, but this should be reassuring if you already take one of these medications.

Tricor appears to clear lung tissue of C19: this research focused on C19’s preference for an environment rich in cholesterol and other fatty acids:

“What they found is that the novel coronavirus prevents the routine burning of carbohydrates, which results in large amounts of fat accumulating inside lung cells – a condition the virus needs to reproduce.”

Tricor reduces those fats, and the researchers claim it is capable of clearing lung tissue of C19 in a matter of days. This was not a clinical trial, however, so more work is needed. Tricor is an FDA approved drug, so it is safe and could be administered “off label” immediately. Tricor is a fibrate; the news with respect to statins and C19 severity is pretty good too! These are not treatments per se, but this should be reassuring if you already take one of these medications.

Hydroxychloroquine works: despite months of carping from media and leftist know-it-all’s dismissing the mere possibility of HCQ as a potential C19 treatment, evidence is accumulating that it is effective in treating early-stage infections after all. The large study conducted by the Henry Ford Health System found that treatment with HCQ early after hospitalization, and with careful monitoring of heart function, cut the death rate in half relative to a control group. Here’s another: an Indian study found that four-plus maintenance doses of HCQ acted as a prophylactic against C19 infection among health care workers, reducing the odds of infection by more than half. An additional piece of evidence is provided by this analysis of a 14-day Swiss ban on the use of HCQ in late May and early June. The ban was associated with a huge leap in the C19 deaths after a lag of less than two weeks. Resumption of HCQ treatment brought C19 deaths down sharply after a similar lag.

Meanwhile, a study in Lancet purporting to show that HCQ was ineffective and posed significant risks to heart health was retracted based on the poor quality of the data.

Remdesivir also cuts death rate: by 62% in a smaller controlled study by the drug maker Gilead Sciences.

Pet ownership might confer some immunity: this one is a little off-beat, and perhaps the research is under-developed, but it is interesting nonetheless!

I owe Instapundit and Marginal Revolution hat tips for several of these items.

Trump Hates/Loves Lockdowns, Dumps on Swedes

07 Sunday Jun 2020

Posted by pnoetx in Health Care, Pandemic

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Tags

Cholesterol, Coronavirus, Donald Trump, Herd Immunity, Institute for Health Metrics and Evaluation, Lockdowns, Nordic, Rose Garden Briefing, Somali Immigration, Sweden, Vitamin D

President Trump was in a festive mood last Friday, pleased with the May employment report, as he should be. But in his Rose Garden word jam, he made some questionable and unnecessary claims about coronavirus policies in the U.S. and the Swedish experience. I credit Trump for pushing to end the lockdowns as it became clear that they were both unhealthy and unsustainable. However, he’s now way too eager to cover his earlier tracks. That is, he is now defensive about the precautions he advocated on the advice of his medical experts in March and early April.

In the Rose Garden, Trump said that lockdowns were necessary to stop the spread of the virus. But to assert that lockdowns “stopped” or even slowed the spread of the virus is speculation at best, and they had deadly effects of their own. Most of the social distancing was achieved through voluntary action, as I have argued previously. Lockdown advocacy lacked any semblance of geographic nuance, as if uniform application makes sense regardless of population density.

Trump went on to say that Sweden was in “bad shape” because it did not impose a lockdown during the pandemic. This is not a new position for the president, but the facts are anything but clear-cut. Again, there is mixed evidence on whether mandatory lockdowns have a real impact on the spread or mortality of the coronavirus (also see here). That’s not to say that social distancing doesn’t work, but much of the benefit comes from private decisions to mitigate risk via distancing. Of course, that also depends on whether people have good information to act on. And to be fair, Sweden did take certain measures such as banning gatherings of more than 50 people, closing schools, and limiting incoming travel.

While the full tale has not been told, and Sweden’s death rate is high on a per capita basis, several other Western European countries that imposed lockdowns have had even higher death rates. The following chart is from the Institute for Health Metrics and Evaluation (IMHE). It is expressed in terms of coronavirus deaths per 100,000 of population. The orange line is Sweden, the purple line is Belgium, and the light blue line is the UK. Actuals are reported through June 4th. While Sweden’s death toll has a somewhat steeper gradient, the level remains well below both Belgium and the UK. It is also lower than the death rates for Italy and Spain, and it is about the same as France’s death rate. Yes, a number of other countries have lower death rates, including the U.S., but the evidence is hardly consistent with Trump’s characterization.

Sweden’s big mistake was not it’s decision to rely on voluntary social distancing, but in failing to adequately protect highly vulnerable populations. The country’s elderly skew older than most countries by several years. Residents of nursing homes have accounted for about half of Sweden’s coronavirus deaths, an international outlier. Inadequate preparedness in elder care has been a particular problem, including a lack of personal protective equipment for workers. There was also a poorly implemented volunteer program, intended to fill-out staffing needs, that appears to have aggravated transmission of the virus.

Sweden has also experienced a concentration of cases and deaths among its large immigrant population. It has the largest immigrant population among the Nordic countries, with large numbers of low income migrants from Syria, Iraq, Iran, Somalia and parts of Eastern Europe. Earlier in the pandemic, according to one estimate, 40% of coronavirus fatalities in Stockholm were in the Somali population. These immigrants tend to live in dense conditions, often in multigenerational households. Many residents with health problems tend to go untreated. Conditions like Vitamin D deficiency and high cholesterol, apparent risk factors for coronavirus severity, likely go untreated in these communities. In addition, language barriers and traditional trust relationships may diminish the effectiveness of communications from public health authorities. In fact, some say the style of Swedish public health messaging was too culturally idiosyncratic to be of much use to immigrants. And one more thing: immigrants are a disproportionately high 28% of nursing home staff in Sweden, implying an intimacy between two vulnerable populations that almost surely acts as a risk multiplier in both.

It might be too harsh to suggest that that Sweden could have prevented the outsized impact of the virus on immigrants. However, Sweden’s coronavirus testing has not been as intensive as other Nordic countries. More testing might have helped alleviate the spread of the virus in nursing homes and in immigrant communities. But the vulnerabilities of the immigrant population might be more a matter of inadequate health care than anything else, both on the demand and supply sides.

Contrary to Trump’s characterization, Sweden’s herd immunity strategy is not the reason for it’s relatively high death rate from the virus. Several countries that imposed lockdowns have had higher death rates. And Sweden’s death rate has been heavily concentrated among the aged in nursing homes and its large immigrant population. It’s possible that Sweden’s approach led to a cavalier attitude with respect identifying vulnerable groups and taking measures that could have protected them, including more intensive testing. Nevertheless, it’s inaccurate and unfair to scapegoat Sweden for not imposing a mandatory lockdown. The choice is not merely whether to impose lockdowns, but how to protect vulnerable populations at least cost. In that sense, general lockdowns are a poor choice.

 

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