[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.