[M T]

Sorry for the shotgun approach.  I found these interesting, but didn't feel each deserved its own thread.  (In response to the Where do you get your news question, I've recently been scanning "COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv")

Remember, these are not peer reviewed and not yet published.

---

(I lead with one that will get your attention, but do scan through them all.)

From Australian authors: "America Addresses Two Epidemics: Cannabis and Coronavirus and their Interactions: An Ecological Geospatial Study"

Cannabis smoking is linked with poor respiratory health, immunosuppression and multiple contaminants. ... Cigarettes were implicated with disease severity in Wuhan, China. ...

Data indicate coronavirus incidence rate (CVIR) demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation. Recent cannabis use is independently predictive of CVIR in bivariate and multivariable adjusted models and intensity of use is interactively significant.

---

Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals Broad Potential Host Range of SARS-CoV-2

Functional assays showed that 44 of these mammalian ACE2 orthologs, including domestic animals, pet animals, livestock animals and even animals in the zoo or aquaria, could bind viral spike protein and support SARS-CoV-2 entry.

lions & tigers & bears,
sea lions & whales,
horses, cattle, sheep, goats, pigs, ....

---

"No test is better than a bad test": Impact of diagnostic uncertainty in mass testing on the spread of Covid-19

regarding the issues of specificity & sensitivity of tests relative to opening up the UK

Findings: Diagnostic uncertainty [of test results] can have a large effect on the epidemic dynamics of Covid-19 within the UK. The dynamics of the epidemic are more sensitive to test performance and targeting than test capacity. The quantity of tests is not a substitute for an effective strategy. Poorly targeted testing has the propensity to exacerbate the peak in infections.
Interpretation: The assessment that 'no test is better than a bad test' is broadly supported by the present analysis. Antibody testing is unlikely to be a solution to the lock-down, regardless of test quality or capacity. A well designed active viral testing strategy combined with incremental relaxation of the lock-down measures is shown to be a potential strategy to restore some social activity whilst continuing to keep infections low.

---

Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data

We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans.
Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average 9.79 YLL.
Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

---

Impacts of Early Interventions on the Age-Specific Incidence of COVID-19in New York, Los Angeles, Daegu and Nairobi

Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities.  The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections.

[M T]

Sorry for the shotgun approach.  I found these interesting, but didn't feel each deserved its own thread.  (In response to the Where do you get your news question, I've recently been scanning "COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv")

Remember, these are not peer reviewed and not yet published.

---

(I lead with one that will get your attention, but do scan through them all.)

From Australian authors: "America Addresses Two Epidemics: Cannabis and Coronavirus and their Interactions: An Ecological Geospatial Study"

Cannabis smoking is linked with poor respiratory health, immunosuppression and multiple contaminants. ... Cigarettes were implicated with disease severity in Wuhan, China. ...

Data indicate coronavirus incidence rate (CVIR) demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation. Recent cannabis use is independently predictive of CVIR in bivariate and multivariable adjusted models and intensity of use is interactively significant.

---

Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals Broad Potential Host Range of SARS-CoV-2

Functional assays showed that 44 of these mammalian ACE2 orthologs, including domestic animals, pet animals, livestock animals and even animals in the zoo or aquaria, could bind viral spike protein and support SARS-CoV-2 entry.

lions & tigers & bears,
sea lions & whales,
horses, cattle, sheep, goats, pigs, ....

---

"No test is better than a bad test": Impact of diagnostic uncertainty in mass testing on the spread of Covid-19

regarding the issues of specificity & sensitivity of tests relative to opening up the UK

Findings: Diagnostic uncertainty [of test results] can have a large effect on the epidemic dynamics of Covid-19 within the UK. The dynamics of the epidemic are more sensitive to test performance and targeting than test capacity. The quantity of tests is not a substitute for an effective strategy. Poorly targeted testing has the propensity to exacerbate the peak in infections.
Interpretation: The assessment that 'no test is better than a bad test' is broadly supported by the present analysis. Antibody testing is unlikely to be a solution to the lock-down, regardless of test quality or capacity. A well designed active viral testing strategy combined with incremental relaxation of the lock-down measures is shown to be a potential strategy to restore some social activity whilst continuing to keep infections low.

---

Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data

We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans.
Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average 9.79 YLL.
Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

---

Impacts of Early Interventions on the Age-Specific Incidence of COVID-19in New York, Los Angeles, Daegu and Nairobi

Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities.  The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections.

[stupac2]

Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data

We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans.

Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average 9.79 YLL.

Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

The country-wide number doesn't seem so bad, although the percentage heavily affected is more than I would've naively guessed. I wonder what a similar number for the great recession would be, a quick google only turned up the article (which we've discussed here before) claiming that mortality during the recession actually decreased, which seems to run counter to this one.

[stupac2]

Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data

We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans.

Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average 9.79 YLL.

Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

The country-wide number doesn't seem so bad, although the percentage heavily affected is more than I would've naively guessed. I wonder what a similar number for the great recession would be, a quick google only turned up the article (which we've discussed here before) claiming that mortality during the recession actually decreased, which seems to run counter to this one.

[M T]

Another set of recent preprints that I thought may be of interest

---

I'd wait for this result (that I highlighted) to be confirmed elsewhere, but it is interesting.
Hypertension and Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19

Among 3017 hospitalized COVID-19 patients, 1584 (52.5%) carried a diagnosis of hypertension. In the discharged or deceased cohort, the overall mortality was significantly increased at 35% vs 13% among COVID-19 patients with hypertension. However, when adjusted for age, the effect of hypertension on mortality was greatly diminished, with a reduction in odds-ratio by over half; and completely disappeared when adjusted for other major covariates. The mortality rates were lower for hypertensive patients prescribed ACE1 (27%, p=0.001) or ARBs (33%, p=0.12) compared to other anti-hypertensive agents (39%) in the unadjusted analyses.

---

This is NOT SARS-CoV-2, but about the same class of viruses (beta-coronoavirus)
Direct observation of repeated infections with endemic coronaviruses
(This study is also discussed in TWiV 607)
Roughly, 10% of beta-coronavirus infections were followed by repeat infections within a year.

This study provides evidence that re-infections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

---

Estimation of SARS-CoV-2 emissions from non-symptomatic cases

Based on models, the study simulated the quantity of virus in the air in a small office or exam room, for asymptomatic cases for breathing alone or for coughing.  Coughing always lead to high numbers (10.9K/cm3 average, 365K/cm3 max) while breathing led to noticeable numbers (0.3/cm3 avg, 11.5/cm3 max).

(Obviously variable for individuals & situations, but roughly 500 cm3 per breath, 15 breaths/min = 7,500 cm3 per minute.)

---

Modifiable and non-modifiable risk factors for COVID-19: results from UK Biobank

Among 428,225 participants [in UK Biobank], 340 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index (RR 1.24 per SD increase), smoking (RR 1.38), slow walking pace as a proxy for physical fitness (RR 1.66) and use of blood pressure medications as a proxy for hypertension (RR 1.40). Non-modifiable risk factors included older age (RR 1.10 per 5 years), male sex (RR 1.64), black ethnicity (RR 1.86), socioeconomic deprivation (RR 1.26 per SD increase in Townsend Index), longstanding illness (RR 1.38) and high cystatin C (RR 1.24 per 1 SD increase).  

To reduce bias, we excluded from the study all participants known to have died COVID-19 pandemic.

So, the risk here was for being diagnosed with the disease, not to die from it.   Interesting to compare the risk-ratio for hypertension here, with the assessment above, which was for dying.

---

Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers

A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. ...
Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05)

---

From UCSF:  CovidCounties.org

CovidCounties - an interactive, real-time tracker of the COVID-19 pandemic at the level of US counties

---

False positives in reverse transcription PCR testing for SARS-CoV-2

Review of external quality assessments [for PCR tests 2005-2019] revealed false positive rates of 0-16.7%, with an interquartile range of 0.8-4.0%  Such rates would have large impacts on test data when prevalence is low. Inclusion of such rates significantly alters four published analyses of population prevalence and asymptomatic ratio.
The high false discovery rate that results, when prevalence is low, from false positive rates typical of RT-PCR assays of RNA viruses raises questions about the usefulness of mass testing; and indicates that across a broad range of likely prevalences, positive test results are more likely to be wrong than are negative results, contrary to public health advice about SARS-CoV-2 testing

---

Estimates of the ongoing need for social distancing and control measures post-"lockdown" from trajectories of COVID-19 cases and mortality.

By fitting regression models to publically available data on daily numbers of newly-confirmed cases and mortality, trajectories, doubling times and reproduction number (R0) were estimated both before and under the control measures. These data ran up to 21st April 2020, and covered 67 countries that had provided sufficient data for modelling. The estimates of R0, before lockdown, based on these data were broadly consistent with those previously published at between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with Spain having the most rapid reductions - R0 0.71 (95%CI 0.65-0.78) based on cases and 0.81 (95%CI 0.77-0.85) based on mortality

Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increase freedom and economic activity. These data suggest that few countries could have even one week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries. . . .

[USA R0 based on confirmed cases: Before lockdown 3.6; After: 0.97; Based on deaths: Before 3.2; After: 1.3]
The best estimate for the USA would seem to be that less than two weeks off each year will be possible if no additional social distancing or isolation measures were introduced.

[M T]

Another set of recent preprints that I thought may be of interest

---

I'd wait for this result (that I highlighted) to be confirmed elsewhere, but it is interesting.
Hypertension and Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19

Among 3017 hospitalized COVID-19 patients, 1584 (52.5%) carried a diagnosis of hypertension. In the discharged or deceased cohort, the overall mortality was significantly increased at 35% vs 13% among COVID-19 patients with hypertension. However, when adjusted for age, the effect of hypertension on mortality was greatly diminished, with a reduction in odds-ratio by over half; and completely disappeared when adjusted for other major covariates. The mortality rates were lower for hypertensive patients prescribed ACE1 (27%, p=0.001) or ARBs (33%, p=0.12) compared to other anti-hypertensive agents (39%) in the unadjusted analyses.

---

This is NOT SARS-CoV-2, but about the same class of viruses (beta-coronoavirus)
Direct observation of repeated infections with endemic coronaviruses
(This study is also discussed in TWiV 607)
Roughly, 10% of beta-coronavirus infections were followed by repeat infections within a year.

This study provides evidence that re-infections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

---

Estimation of SARS-CoV-2 emissions from non-symptomatic cases

Based on models, the study simulated the quantity of virus in the air in a small office or exam room, for asymptomatic cases for breathing alone or for coughing.  Coughing always lead to high numbers (10.9K/cm3 average, 365K/cm3 max) while breathing led to noticeable numbers (0.3/cm3 avg, 11.5/cm3 max).

(Obviously variable for individuals & situations, but roughly 500 cm3 per breath, 15 breaths/min = 7,500 cm3 per minute.)

---

Modifiable and non-modifiable risk factors for COVID-19: results from UK Biobank

Among 428,225 participants [in UK Biobank], 340 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index (RR 1.24 per SD increase), smoking (RR 1.38), slow walking pace as a proxy for physical fitness (RR 1.66) and use of blood pressure medications as a proxy for hypertension (RR 1.40). Non-modifiable risk factors included older age (RR 1.10 per 5 years), male sex (RR 1.64), black ethnicity (RR 1.86), socioeconomic deprivation (RR 1.26 per SD increase in Townsend Index), longstanding illness (RR 1.38) and high cystatin C (RR 1.24 per 1 SD increase).  

To reduce bias, we excluded from the study all participants known to have died COVID-19 pandemic.

So, the risk here was for being diagnosed with the disease, not to die from it.   Interesting to compare the risk-ratio for hypertension here, with the assessment above, which was for dying.

---

Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers

A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. ...
Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05)

---

From UCSF:  CovidCounties.org

CovidCounties - an interactive, real-time tracker of the COVID-19 pandemic at the level of US counties

---

False positives in reverse transcription PCR testing for SARS-CoV-2

Review of external quality assessments [for PCR tests 2005-2019] revealed false positive rates of 0-16.7%, with an interquartile range of 0.8-4.0%  Such rates would have large impacts on test data when prevalence is low. Inclusion of such rates significantly alters four published analyses of population prevalence and asymptomatic ratio.
The high false discovery rate that results, when prevalence is low, from false positive rates typical of RT-PCR assays of RNA viruses raises questions about the usefulness of mass testing; and indicates that across a broad range of likely prevalences, positive test results are more likely to be wrong than are negative results, contrary to public health advice about SARS-CoV-2 testing

---

Estimates of the ongoing need for social distancing and control measures post-"lockdown" from trajectories of COVID-19 cases and mortality.

By fitting regression models to publically available data on daily numbers of newly-confirmed cases and mortality, trajectories, doubling times and reproduction number (R0) were estimated both before and under the control measures. These data ran up to 21st April 2020, and covered 67 countries that had provided sufficient data for modelling. The estimates of R0, before lockdown, based on these data were broadly consistent with those previously published at between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with Spain having the most rapid reductions - R0 0.71 (95%CI 0.65-0.78) based on cases and 0.81 (95%CI 0.77-0.85) based on mortality

Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increase freedom and economic activity. These data suggest that few countries could have even one week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries. . . .

[USA R0 based on confirmed cases: Before lockdown 3.6; After: 0.97; Based on deaths: Before 3.2; After: 1.3]
The best estimate for the USA would seem to be that less than two weeks off each year will be possible if no additional social distancing or isolation measures were introduced.

[M T]

The effects of ARBs, ACEIs and statins on clinical outcomes of COVID-19 infection among nursing home residents

We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 infection (unadjusted OR 2.91; CI 1.27-6.71; p=0.011), which remained statistically significant after adjusting for age, sex, functional status, diabetes mellitus and hypertension. The strength of this association was considerable and clinically important. Although the effects of statin intake on serious clinical outcome (long-stay hospitalisation or death) were in the same beneficial direction, these were not statistically significant...
here was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 1.52; CI 0.62-3.50; p=0.339) or serious clinical outcome (OR 0.79; CI 0.26-1.95; p=0.629)

The role of high cholesterol in age-related COVID19 lethality
Argues that high cholesterol levels in tissue (vs blood) gives a larger & more entry points.

NON-WHITE ETHNICITY, MALE SEX, AND HIGHER BODY MASS INDEX, BUT NOT MEDICATIONS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ARE ASSOCIATED WITH CORONAVIRUS DISEASE 2019 (COVID-19) HOSPITALISATION: REVIEW OF THE FIRST 669 CASES FROM THE UK BIOBANK

We considered the following exposures: age, sex, ethnicity, body mass index (BMI), diabetes, hypertension, hypercholesterolaemia, ACEi/ARB use, prior myocardial infarction (MI), and smoking. . . . Among participants tested for COVID-19 with presumed moderate to severe symptoms in a hospital setting, non-white ethnicity, male sex, and higher BMI are associated with a positive result. Other cardiometabolic morbidities confer increased risk of hospitalisation, without specificity for COVID-19. Notably, ACE/ARB use did not associate with COVID-19 status.

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well.

Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population Shows Low Rates of Positivity
In Seattle, less than 1% of asymptomatic patients were positive.

Estimating pre-symptomatic transmission of COVID-19: a secondary analysis using published data

Proportion of pre-symptomatic transmission ranged from 33.7% in Wuhan to 72.7% in Hong Kong . . .
Our work suggests that transmission of SARS-CoV-2 is most likely in the day before symptom onset whereas estimates suggesting most pre-symptomatic transmission highlighted a mean transmission times almost 3 days before symptom onset.

Bidirectional contact tracing is required for reliable COVID-19 control
Modeling suggests that contact tracing is more effective if it finds the source infector as well as the infectees.  "as long as exposure events can be detected by nearly all smartphones, the combination of manual and digital with bidirectional tracing more than doubles the probability of controlling outbreaks across three epidemiological scenarios."

Correlation between prevalence of tobacco smoking and risk and severity of COVID-19 at the national level in the European Union: an ecological study.

We have found that there is a statistically significant negative correlation between the age-standardized prevalence of tobacco smoking and the attack rate of COVID-19 in member states of the EU

I saw other studies that indicated smoking was associate with less disease.

Moving Beyond a Peak Mentality: Plateaus, Shoulders, Oscillations and Other 'Anomalous' Behavior-Driven Shapes in COVID-19 Outbreaks

Here we explore a model of fatality-driven awareness in which individual protective measures increase with death rates. . . .
We also show that incorporating long-term awareness can avoid peak resurgence and accelerate epidemic decline. We suggest that awareness of the severity of the short- and long-term epidemic is likely to play a critical role in disease dynamics, beyond that imposed by intervention-driven policies.

Infection fatality rate of SARS-CoV-2 infection in a German community with a super-spreading event
Testing of households 6 weeks after a carnival

Of the 919 individuals with evaluable infection status (out of 1,007; 405 households) 15.5% (95% CI: [12.3%; 19.0%]) were infected. This is 5-fold higher than the number of officially reported cases for this community (3.1%). Infection was associated with characteristic symptoms such as loss of smell and taste. 22.2% of all infected individuals were asymptomatic. . . .
Age and sex were not found to be associated with the infection rate. Participation in carnival festivities increased both the infection rate (21.3% vs. 9.5%, p<0.001) and the number of symptoms in the infected (estimated relative mean increase 1.6, p=0.007). The risk of a person being infected was not found to be associated with the number of study participants in the household this person lived in.

[M T]

The effects of ARBs, ACEIs and statins on clinical outcomes of COVID-19 infection among nursing home residents

We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 infection (unadjusted OR 2.91; CI 1.27-6.71; p=0.011), which remained statistically significant after adjusting for age, sex, functional status, diabetes mellitus and hypertension. The strength of this association was considerable and clinically important. Although the effects of statin intake on serious clinical outcome (long-stay hospitalisation or death) were in the same beneficial direction, these were not statistically significant...
here was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 1.52; CI 0.62-3.50; p=0.339) or serious clinical outcome (OR 0.79; CI 0.26-1.95; p=0.629)

The role of high cholesterol in age-related COVID19 lethality
Argues that high cholesterol levels in tissue (vs blood) gives a larger & more entry points.

NON-WHITE ETHNICITY, MALE SEX, AND HIGHER BODY MASS INDEX, BUT NOT MEDICATIONS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ARE ASSOCIATED WITH CORONAVIRUS DISEASE 2019 (COVID-19) HOSPITALISATION: REVIEW OF THE FIRST 669 CASES FROM THE UK BIOBANK

We considered the following exposures: age, sex, ethnicity, body mass index (BMI), diabetes, hypertension, hypercholesterolaemia, ACEi/ARB use, prior myocardial infarction (MI), and smoking. . . . Among participants tested for COVID-19 with presumed moderate to severe symptoms in a hospital setting, non-white ethnicity, male sex, and higher BMI are associated with a positive result. Other cardiometabolic morbidities confer increased risk of hospitalisation, without specificity for COVID-19. Notably, ACE/ARB use did not associate with COVID-19 status.

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well.

Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population Shows Low Rates of Positivity
In Seattle, less than 1% of asymptomatic patients were positive.

Estimating pre-symptomatic transmission of COVID-19: a secondary analysis using published data

Proportion of pre-symptomatic transmission ranged from 33.7% in Wuhan to 72.7% in Hong Kong . . .
Our work suggests that transmission of SARS-CoV-2 is most likely in the day before symptom onset whereas estimates suggesting most pre-symptomatic transmission highlighted a mean transmission times almost 3 days before symptom onset.

Bidirectional contact tracing is required for reliable COVID-19 control
Modeling suggests that contact tracing is more effective if it finds the source infector as well as the infectees.  "as long as exposure events can be detected by nearly all smartphones, the combination of manual and digital with bidirectional tracing more than doubles the probability of controlling outbreaks across three epidemiological scenarios."

Correlation between prevalence of tobacco smoking and risk and severity of COVID-19 at the national level in the European Union: an ecological study.

We have found that there is a statistically significant negative correlation between the age-standardized prevalence of tobacco smoking and the attack rate of COVID-19 in member states of the EU

I saw other studies that indicated smoking was associate with less disease.

Moving Beyond a Peak Mentality: Plateaus, Shoulders, Oscillations and Other 'Anomalous' Behavior-Driven Shapes in COVID-19 Outbreaks

Here we explore a model of fatality-driven awareness in which individual protective measures increase with death rates. . . .
We also show that incorporating long-term awareness can avoid peak resurgence and accelerate epidemic decline. We suggest that awareness of the severity of the short- and long-term epidemic is likely to play a critical role in disease dynamics, beyond that imposed by intervention-driven policies.

Infection fatality rate of SARS-CoV-2 infection in a German community with a super-spreading event
Testing of households 6 weeks after a carnival

Of the 919 individuals with evaluable infection status (out of 1,007; 405 households) 15.5% (95% CI: [12.3%; 19.0%]) were infected. This is 5-fold higher than the number of officially reported cases for this community (3.1%). Infection was associated with characteristic symptoms such as loss of smell and taste. 22.2% of all infected individuals were asymptomatic. . . .
Age and sex were not found to be associated with the infection rate. Participation in carnival festivities increased both the infection rate (21.3% vs. 9.5%, p<0.001) and the number of symptoms in the infected (estimated relative mean increase 1.6, p=0.007). The risk of a person being infected was not found to be associated with the number of study participants in the household this person lived in.

[Snorlax94]

Another set of recent preprints that I thought may be of interest
This is NOT SARS-CoV-2, but about the same class of viruses (beta-coronoavirus)
Direct observation of repeated infections with endemic coronaviruses
(This study is also discussed in TWiV 607)
Roughly, 10% of beta-coronavirus infections were followed by repeat infections within a year.

This study provides evidence that re-infections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

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Estimation of SARS-CoV-2 emissions from non-symptomatic cases

Based on models, the study simulated the quantity of virus in the air in a small office or exam room, for asymptomatic cases for breathing alone or for coughing.  Coughing always lead to high numbers (10.9K/cm3 average, 365K/cm3 max) while breathing led to noticeable numbers (0.3/cm3 avg, 11.5/cm3 max).

(Obviously variable for individuals & situations, but roughly 500 cm3 per breath, 15 breaths/min = 7,500 cm3 per minute.)

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Thanks, MT! I appreciate you highlighting these.

The article in repeat infections of coronaviruses goes on to say:

“In contrast, an experimental study on murine coronavirus (MHV), which produces severe, systemic infections in mice, has shown an interplay between virus-specific antibodies and T cells, that upon survival in the host lead to life-long protection against reinfection [18]. Similarly, a longer immunity profile has been hypothesized for SARS and MERS due to their increased severity and to the systemic response that infection induces [14]. Specific antibodies were detectable for at least 2 years in SARS and MERS survivors [19] [20]. Although longitudinal studies on SARS survivors have not detected specific SARS IGG antibody persistence 5 years after infection, they have found that specific memory T cells persist in the peripheral blood of recovered SARS patients, and at higher levels in patients who experienced severe disease [21]. Whether the presence of these memory T cells would be enough to induce a fast, protective response upon reinfection with SARS has not been assessed.”

So hopefully that bodes well for Covid-19.

[Snorlax94]

Another set of recent preprints that I thought may be of interest
This is NOT SARS-CoV-2, but about the same class of viruses (beta-coronoavirus)
Direct observation of repeated infections with endemic coronaviruses
(This study is also discussed in TWiV 607)
Roughly, 10% of beta-coronavirus infections were followed by repeat infections within a year.

This study provides evidence that re-infections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

---

Estimation of SARS-CoV-2 emissions from non-symptomatic cases

Based on models, the study simulated the quantity of virus in the air in a small office or exam room, for asymptomatic cases for breathing alone or for coughing.  Coughing always lead to high numbers (10.9K/cm3 average, 365K/cm3 max) while breathing led to noticeable numbers (0.3/cm3 avg, 11.5/cm3 max).

(Obviously variable for individuals & situations, but roughly 500 cm3 per breath, 15 breaths/min = 7,500 cm3 per minute.)

---

Thanks, MT! I appreciate you highlighting these.

The article in repeat infections of coronaviruses goes on to say:

“In contrast, an experimental study on murine coronavirus (MHV), which produces severe, systemic infections in mice, has shown an interplay between virus-specific antibodies and T cells, that upon survival in the host lead to life-long protection against reinfection [18]. Similarly, a longer immunity profile has been hypothesized for SARS and MERS due to their increased severity and to the systemic response that infection induces [14]. Specific antibodies were detectable for at least 2 years in SARS and MERS survivors [19] [20]. Although longitudinal studies on SARS survivors have not detected specific SARS IGG antibody persistence 5 years after infection, they have found that specific memory T cells persist in the peripheral blood of recovered SARS patients, and at higher levels in patients who experienced severe disease [21]. Whether the presence of these memory T cells would be enough to induce a fast, protective response upon reinfection with SARS has not been assessed.”

So hopefully that bodes well for Covid-19.