COVID19 update, June 14, 2020: avoiding the Three C’s of Transmission; most asymptomatic cases remain asymptomatic

Busy workday, so just some quick updates:

(1) (hat tip: Masgramondou): Are Technica: “Just 10-20% of cases are behind 80% of transmission” 

Benjamin Cowling, a Hong Kong-based epidemiologist and biostatistics expert, agrees. Cowling and colleagues recently studied transmission in Hong Kong, finding superspreading events drove local transmission. In a recent op-ed, he and a colleague argue that public health policies aimed at stopping the pandemic should focus on stopping superspreading.

“The epidemic’s growth can be controlled with tactics far less disruptive, socially and economically, than the extended lockdowns or other extreme forms of social distancing that much of the world has experienced over the past few months,” the researchers wrote

In an email to Ars, Cowling fleshed out this idea a bit, noting that “measures that specifically target superspreading are those that reduce or prevent large gatherings of people,” such as those to reduce the density of people in schools and workplaces.

Measures not specifically targeted to superspreading, he noted, “are those like asking everybody to stay at home as much as they can, despite many workplaces and social settings not being places that superspreading could occur.”

In the op-ed, Cowling noted that Japan—which has been relatively successful at managing the pandemic—has employed an anti-superspreading policy called [“the Three Cs Of Transmission”]: Avoid (1) Closed spaces with poor ventilation, (2) Crowded places, and (3) Close-contact settings, such as close-range conversations. The risk for superspreading is highest in situations with all three Cs.

[…]Cowling and his colleagues’ analysis has been posted online but has not yet been peer-reviewed or published in a scientific journal. But, they note, their findings from Hong Kong aren’t unique. For instance, a study published in the Lancet in April, which looked at transmission of SARS-CoV-2 in Shenzhen, China, found that just around 9 percent of cases accounted for 80 percent of transmission. And a modeling study from researchers in London likewise found that just about 10 percent of cases may account for 80 percent of transmission.

Read the whole thing.

(2) via Instapundit, this report by UPI quoting this letter to the New England Journal of Medicine from a Japanese team:

http://doi.org/10.1056/NEJMc2013020

The outbreak of coronavirus disease 2019 (Covid-19) on the cruise ship Diamond Princess led to 712 persons being infected with SARS-CoV-2 among the 3711 passengers and crew members, and 410 (58%) of these infected persons were asymptomatic at the time of testing[….] A total of 96 persons infected with SARS-CoV-2 who were asymptomatic at the time of testing, along with their 32 cabinmates who tested negative on the ship, were transferred from the Diamond Princess to a hospital in central Japan between February 19 and February 26 for continued observation. Clinical signs and symptoms of Covid-19 subsequently developed in 11 of these 96 persons, a median of 4 days (interquartile range, 3 to 5; range, 3 to 7) after the first positive polymerase-chain-reaction (PCR) test, which meant that they had been presymptomatic rather than asymptomatic.

[…] The group of persons with asymptomatic SARS-CoV-2 infection consisted of 58 passengers and 32 crew members, with median age of 59.5 years (interquartile range, 36 to 68; range, 9 to 77). A total of 24 of these persons (27%) had coexisting medical conditions, including hypertension (in 20%) and diabetes (9%). The first PCR test at the hospital was performed a mean of 6 days after the initial positive PCR test on the ship. The median number of days between the first positive PCR test (either on the ship or at the hospital) and the first of the two serial negative PCR tests was 9 days (interquartile range, 6 to 11; range, 3 to 21), and the cumulative percentages of persons with resolution of infection 8 and 15 days after the first positive PCR test were 48% and 90%, respectively. The risk of delayed resolution of infection increased with increasing age.

In this cohort, the majority of asymptomatically infected persons remained asymptomatic throughout the course of the infection. The time to the resolution of infection increased with increasing age.

 

(3) UnHerd: so where did the virus really come from? Dogmatic answers do not behoove a scientist, as the writer rightly argues. On the other hand, extraordinary claims (e.g., a genetically engineered virus) require extraordinary proof. Either way, we need all the evidence we can get. Read the whole article.

This is in the realm of speculation, but I’ve been wondering: what if, after the outbreak began, local officials panicked thinking this may be a human-“improved” virus that had escaped from the WiV, then calmed down once it became clear it was “only” another novel coronavirus. That would explain some of the skittish behavior in the very beginning, the destruction of samples,…  

ADDENDUM: yes, public health experts are undermining themselves by U-turning on recommendations for political expedience. 

And Insta snarks “nothing to see here, move along”: Parts of Beijing locked down due to fresh virus cluster

ADDENDUM 2: Israeli public health expert on what we might face in the winter 

COVID19 update, May 31, 2020: which patients benefit most from Remdesivir; asymptomatic infection rate; the post-lockdown economy; miscellaneous updates

(1) Dr. Seheult discusses remdesivir for different categories of patients, and suggests that the drug is most beneficial (in terms of quicker recovery) for patients sick enough to require oxygen, but not so sick as to require mechanical ventilation or ECMOs (“heart-lung machines”). In this latter group, the virus has already done so much damage that remdesivir amounts to “closing the barn door after the horses have fled”, while mild cases will resolve on their own.

The conventional division of patients is (averaged across age groups):

  • 80% self-limiting, self-resolving disease
  • 15% get more severely ill
  • 5% critically ill

So it would be the 15% where the drug can make most of the difference, probably by keeping patients from moving into the 5% critical group. 

(2) Dr. John Campbell’s video looks at the asymptomatic infection rate, which he frustratingly places “between 5% and 80%”, and briefly highlights different studies that arrive at wildly different rates. My working assumption all along has been “about 50%”. 

(3) The Economist has a somewhat pessimistic take on the post-lockdown economy. Note that at least some of the economic effects of the pandemic are also felt in countries that never locked down, like Sweden.

Relatedly, Die Welt (in German) looks at how in reopened Germany, spending habits have changed to the extent that some retailers say they don’t see the point of reopening. The main shopping streets have seen foot traffic dwindle by 30 to 75% (Berlin’s famous Kurfürstendamm was hardest hit). Stores with an online presence, who kept in touch with customers during the crisis, have weathered the storm better, while some with a primarily online business model have seen revenue rise (including a new online grocery shopping chain).

(3) Miscellaneous updates:

Moderna’s COVID-19 vaccines now moves into Phase 2 clinical trials, reports the Jerusalem Post, who also note that the chief scientific officer of Moderna is an expat Israeli. (Like in information technology, tiny Israel punches well above its weight in biotech.)

Forbes highlights what it calls the most important COVID-19 statistic: 42% of US deaths occur in a group that is just 0.6% pf the US population, namely care home residents.

Oddly enough: Monkeys steal COVID-19 testing samples in India. 

Tangentially related, the Daily Telegraph looks at what awaits Hong Kong under full ChiCom rule. The UK has offered asylum to Hong Kongers who still hold BNO (British National Overseas) passports. (This unusual type of passport does not come with automatic “right of abode” in the UK.)

COVID19 update, May 28, 2020: ACE inhibitors beneficial; asymptomatic infection rate as high as 80%; NYT on California economy in freefall

(1) The lead story of Chemical and Engineering News, the house organ of the American Chemical Society, is about rethinking the role of ACE inhibitors (angiotensin converting enzyme inhibitors, a commonly used family of blood pressure drugs).

https://cendigitalmagazine.acs.org/2020/05/22/rethinking-the-role-of-blood-pressure-drugs-in-covid-19/content.html

“Once thought to boost levels of ACE2 , the novel coronavirus’s doorway into human cells, these widely used medicines are now contenders to treat the respiratory disease”

(2) Meanwhile,  the Daily Telegraph has a popular write-up of an intriguing paper that just appeared in Thorax, a daughter journal of the British Medical Journal. It suggests the asymptomatic infection rate may be much higher than the 35% in the revised CDC figures

http://doi.org/10.1136/thoraxjnl-2020-215091

ABSTRACT: We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic. Of the 217 passengers and crew on board, 128 tested positive for COVID-19 on reverse transcription–PCR (59%). Of the COVID-19-positive patients, 19% (24) were symptomatic; 6.2% (8) required medical evacuation; 3.1% (4) were intubated and ventilated; and the mortality was 0.8% (1). The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients). We conclude that the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.

The Uruguayan Ministry of Health provided on board SARS-CoV-2 virus testing of all passengers and crew, which occurred on 3 April (day 20; Atgen-Diagnostica, Montevideo) with CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel.

In the body text we find that: 

 

[The 128 who tested positive on RT-PCR]  included all passengers who tested negative on the VivaDiag qSARS-CoV-IgM/IgG Rapid [antibody] Test. There were 10 instances where two passengers sharing a cabin recorded positive and negative results.

[…]

From the departure date in mid-March 2020 and for the next 28 days, the expedition cruise ship had no outside human contact and was thus a totally isolated environment in this sense. […]

[…]

We conclude from this observational study that

  • The prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.
  • Rapid  [antibody] COVID-19 testing of patients in the acute phase is unreliable.
  • The majority of COVID-19-positive patients were asymptomatic (81%).
  • The presence of discordant COVID-19 results in numerous cabins suggests that there may be a significant false-negative rate with RT-PCR testing. Follow-up testing is being performed to determine this.
  • The timing of symptoms in some passengers (day 24) suggests that there may have been cross contamination after cabin isolation.

 

Just how reliable is RT-PCR really?  According to this piece in IEEE Spectrum, current test setups reach are essentially 100% sensitive (no false negatives) and 96% specific (4% false positives) with lab-generated samples., i.e., if you feed them virus cultures. The trouble begins when you have to collect specimens from actual patients.  According to this piece in MD Magazine,   “Of the specimens collected [from known COVID-19 patients], bronchoalveolar lavage fluid specimens demonstrated the highest positive rates of at 93% (n = 14). This was followed by sputum at 72% (n = 75), nasal swabs at 63% (n = 5), fibrobronchoscope brush biopsy at 46% (6/13), pharyngeal swabs at 32% (n = 126), feces at 29% (n = 44) and blood at 1% (n = 3). The authors of that study pointed out that testing of specimens from multiple sites may improve the sensitivity and reduce false-negative test results.” 

 

(3) Via David Bernstein: the WSJ on New York’s long road to recovery even after a lifting of the lockdown. (Archived copy here.)

And via Instapundit, the NYTimes on The price of a lockdown: economic freefall in California

(archived copy ) To be fair, the tourism industry would have been bludgeoned with or without a lockdown, as the (proportionally less important) Swedish tourism sector has learned.

But a large part of the rest could have been mitigated, and can still be mitigated, by not going the “37-step reopening over 10 years” route in California.  (Heck, when did The Babylon Bee forget it was a satirical publication?) But — as much as this sickens even the jaded student of history — I suspect that for some politicians, ensuring that the recovery does not happen before November is worth any price…  

 

Finally, to my Jewish readers, happy Shavuot! There will probably not be an edition on the holiday unless breaking developments warrant it.

 

ADDENDUM: an op-ed in The Lancet in defense of prophylactic use of hydroxychloroquine in India.