COVID-19 in practice

SARS-CoV-2 to its friends

November 25, 2020 — December 7, 2022

count data
stochastic processes
time series
Figure 1

1 Epidemiology of

See also epidemiology, contact tracing.

2 Testing dynamics

Current public health advice boils down to a heuristic that the Rapid Antigen Tests (🐀) are a good proxy for actual contagiousness.

Figure 2: How we hope the rapid antigen tests function, according to ABC News, who claim to have gotten it from a prestigious journal but don’t actually give a reference so you have to take it on faith I guess?
Figure 3: Possible test negativity model for covid variants in 2021, by Jarvis and Kelley

The actual story is complicated and nuanced. Small sample trial, updated for Omicron: Adamson et al. (2022), observes Covid transmission with saliva PCR cycle threshold (Ct) values between 23-28 for the N gene in an \(n=30\) trial. tl;dr: For their tests at least the start of the infection window was not detected by 🐀s (all false negatives.) At the end of the infection, 🐀s produces both false positives and false negatives wrt/ infectiousness. Data here.

Bonus complication: we are possibly using 🐀s wrong, at least for Omicron, if we follow the advice to swab only our noses. Should you add a throat swab to your at-home covid test?. update: This is ambivalently helpful and may even get a false positive (Killingley et al. 2022). Here is a new graph of test efficacy from that study, which was small but well controlled (it was the first challenge trial).

Figure 5: Test specificity in Killingley et al. (2022). Approximately speaking, the black (sensitivity) tells us how likely we are to get a true positive, and the white (specificity) tells us how likely we are to get a true negative, in this cohort of 32 test subjects. The specificity is 100% here because the baseline is PCR.

3 Personal risk calculators

For now, as a good tool for thinking things through (very approximately!) I recommend a microlife-style COVID risk calculator to consider the risk of various activities.

I find it clarifying, although I do not take it literally. Obviously, check the dates and specificity of the data for your region, and bear in mind that it is just an estimator, and written by non-epidemiologists. For example there is something funky about how they account for duration of activities; my risk for catching covid should asymptotically approach a constant as time goes on, but it seems to increase linearly? That approximation is probably fine for many events of interest, but use care in planning long events.

3.1 Airborne transmission

Elizabeth van Nostrand recommends the Bazant lab COVID-19 Indoor Safety Guideline (Bazant and Bush 2021) for a risk calculator for indoor events. Here is the source code for that and here is the model.

See also p Co2 monitoring.

(Burridge et al. 2021; Bazant et al. n.d.; Bazant and Bush 2021)

The backstrocy to how this has been mishandled is fascinating (Randall et al. 2021; C. C. Wang et al. 2021): The 60-Year-Old Scientific Screwup That Helped Covid Kill.

4 Evaluating societal cost

Actuarial lives and quality-adjusted-life-years were not popular for costing public interventions in the pandemic (Hall and Viney 2021). Subhash Pokhrel explains at length Why standard ways of valuing health were set aside during the pandemic. He argues, basically, that we use a risk-averse decision rule to value public interventions as a kind of precautionary principle. Implicitly, this leads us to ask, why did we not do better experiments to reduce uncertainties so we could make that trade-off better? It seemed that uncertainty was extremely expensive and therefore that we had a massive budget to reduce it. This is the platform of organisations like 1Day Sooner who advocate accelerated medical trials by participants who volunteered to be infected. I volunteered for this.

Human challenge trials deliberately expose participants to infection, to study diseases and test vaccines or treatments.

This is cheap talk though. There was not really anywhere to take my volunteer energy in Australia, and thereby prove that I would put my money where my mouth is on this.

Now that we have acquired more precise estimates of COVID dynamics, Paul Dolan and Christian Krekel advocate a return to QALY-like measures in How should we measure the impact of Covid-19 policies on our wellbeing?; There are some nifty links in the citation list.

I am curious about the risk of new variants of COVID and the implications of the new regime. I do not know enough epidemiology or virology to understand the risks we face there, but I suspect it is going to be a classic Black swan tail-risk (Cirillo and Taleb 2020). that is, we want to account for the possibility of large extreme downsides to whatever policies we adopted.

Optimising for Expected QALY is not enough if it comes with a significant risk of extreme QALY loss. That said, the economic consensus is strongly against substantial public health interventions at this stage.

Also, the question of how to trade-off wellbeing, happiness and disease risk is tricky and deep. To read: Dolan and Kahneman (2008) on what hedonism even is.

5 Virulence and risks upon infection

5.1 Death and life years

As measured by lost lifetime, some COVID deaths are crueller than others. When a 90 year old victim with multiple health complaints goes one month earlier to their grave because of COVID, that is sad, but it is not so awful as when a child is cut down decades early. Mercifully, COVID vastly prefers the former case to the latter — it is more likely to scrape some time off the end of a long life than to cut down a short one. So, if some of us die of COVID, how much of my life will it have cost me, on average? Wouterse, Ram, and van Baal (2022) we would have lost 3-4 quality-adjusted life years (QALY) on average. This was before Omicron and may need updating, if the age profile has changed substantially.

5.2 Relative rate compared to normal life risk

We might wonder how much catching COVID adds to your risk rate. Back before Omicron David Spiegelhalter asked How much ‘normal’ risk does Covid represent? and answered (Spiegelhalter 2020)

roughly speaking, we might say that getting COVID-19 is like packing a year’s worth of risk into a week or two.

In fact it is complicated, with slightly more risk for over 55s and much less for 20 school children.

5.3 Long covid

Seems to be real, dammit (Blomberg et al. 2021). Well then, how bad is it? How much risk of it should I tolerate? Elizabeth Van Nostrand argues Long Covid Is Not Necessarily Your Biggest Problem, i.e. that it is a real problem but does not loom particularly large amongst in all the other real problems. Scott Alexander that it looms reasonably large. There has been a methodological update which revises the probability of long covid symptoms down: UK Office for National Statistics: Technical article: Updated estimates of the prevalence of post-acute symptoms among people with coronavirus (COVID-19) in the UK. It is not compactly summarized in that report, but you can scroll down a Zvi Mowshowitz article to find highlights.

As far as long-ish COVID, i.e. all the other non-death inconveniences, a report based on Maltese data (Cuschieri et al. 2021) estimates that 95% of the impact of COVID in Disability-adjusted life years from 2020 is being dead; the remaining 5% is other stuff. The report is also pretty interesting as far as working out how much of the impact of sickness is tiredness after the initial phase etc. They argue that the community impacts of long term COVID are probably somewhat higher than the acute impacts of COVID, although not by much. Worth a read.

TODO: C&C with Long influenza

Figure 6

5.4 Comorbidities

People with Certain Medical Conditions

Body Mass Index and Risk for COVID-19–Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death in the United States, March–December 2020

5.5 Omicron variant

Why are we slow to pump out relative morbidity estimates for the notionally civilisation-defining moment of Omicron dominance?

Best I could find was Lewnard et al. (2022) which doesn’t break out the relative morbidity versus vaccine, except to note omicron sufferers were more likely to be vaccinated than delta sufferers. Across all patients

Omicron variant infections were associated with 52%, 53%, 74%, and 91% reductions in risk of any subsequent hospitalization, symptomatic hospitalization, ICU admission, and mortality, relative to Delta variant infections. Median duration of hospital stay for patients admitted with symptomatic Omicron variant infections was approximately 70% (∼3.4 days) shorter than that observed among patients with symptomatic Delta variant infections.

Realistically, this means we can estimate the mortality risk from Omicron as around 4-5 days of normal risk.

Figure 7: Histories of patients with Omicron (SGTF) versus other which is in practice probably Delta, reproduced from the Lewnard article.

6 Transmission

I need to collect some articles on these theme, when I have a moment to spare.

Which interventions are best? Jeremy Howard summarises lower cost interventions: improved masks, better ventilation, rapid antigen testing.

A cursory inspection of the literature seems to suggest that surface transmission is not worth worrying about (but why not wash your hands?)

Transmission comes down mostly to airflow, afaict. Where are those airborne virions going?

Masking well is hard, but seems to make a difference if you do it well. Evidence for masking lazily (i.e. like a normal human) seems pretty weak.

Distancing is not entirely pointless but effectiveness depends on airflow.

What is easy to do well and makes a difference is ventilation. Do things outside if possible. Do things with the windows open if possible. If the windows don’t open, check that the aircon has a HEPA filter. If the aircon does not have a filter, just get an air purifier. They are not that expensive. I have a Breville the Easy Air Purifier, although I have not assayed its effectiveness against COVID-19 specifically. At AUD229, its ticket price is less than the cost of skipping work for a week due to COVID.

Questions: Does UV air purificaiton do the trick, e.g here is a UVC Air Purifier for HVAC.

Since I have presented these assertions without evidence, please don’t take them on trust. Supporting citations or refutations welcome.

6.1 Modeliing airborne transmission

Is the Wells-Riley model any good? (Noakes and Sleigh 2009; Sze To and Chao 2010).

7 Treating

A contentious area.

Figure 8: David McCandless, Tom Evans, Paul Barton, COVID-19 treatments by evidence level and media attention.. Click through to view full, interactive, version.

There is a reasonably current overview of various options in 11-16-2021_JHMI Clinical Recommendations for Pharmacologic Treatment of COVID-19. Notably includes several off-the-shelf treatments. I’m not even listing the monoclonal antibodies.

7.1 Topical sprays

Various nasal sprays are used for cold and other viruses, some of which might have an effect on COVID (Fais et al. 2022; Friedland et al. 2022; Fröba et al. 2021; Kozlov 2022).

One ingredient which has specific clinical trials for covid Nitric Oxide (salman 2021) which has passed clinical trials (Sanotize Research and Development corp. 2021; Winchester et al. 2021) and been released as a product, Enovid/VirX in a slow-release nasal sppray formuluation.

enovid and VirX are the identical product, branded under different names for marketing in various territories around the world. Nitric Oxide Nasal Spray (NONS) is the generic name of the product.

7.2 Vitamin D

Wow, why is the Vitamin D literature so spammy?

tl;dr; AFAICT the case that Vitamin D is helpful is weak, and the case that it is not hurtful is strong so, take vitamin D if you want.

8 Simulating

9 Current restrictions where I live

Figure 9: The ultimate in COVID-safety

Too confusing, gave up trying to understand. Using own judgment.

10 Tracking Australia’s contagion

11 Incoming

12 References

Adam. 2020. Special Report: The Simulations Driving the World’s Response to COVID-19.” Nature.
Adamson, Sikka, Wyllie, et al. 2022. Discordant SARS-CoV-2 PCR and Rapid Antigen Test Results When Infectious: A December 2021 Occupational Case Series.”
Agrawal, Cantor, Sood, et al. 2021. The Impact of the COVID-19 Pandemic and Policy Responses on Excess Mortality.” w28930.
Arpino, Grossi, Cortellessa, et al. 2022. Risk of SARS-CoV-2 in a Car Cabin Assessed Through 3D CFD Simulations.” Indoor Air.
Banerjee, Pasea, Harris, et al. 2020. Estimating Excess 1-Year Mortality Associated with the COVID-19 Pandemic According to Underlying Conditions and Age: A Population-Based Cohort Study.” The Lancet.
Bazant, and Bush. 2021. A Guideline to Limit Indoor Airborne Transmission of COVID-19.” Proceedings of the National Academy of Sciences.
Bazant, Kodio, Cohen, et al. n.d. Monitoring Carbon Dioxide to Quantify the Risk of Indoor Airborne Transmission of COVID-19.” Flow.
Berwanger. 2022. Fluvoxamine for outpatients with COVID-19: where do we stand? The Lancet Global Health.
Blomberg, Mohn, Brokstad, et al. 2021. Long COVID in a Prospective Cohort of Home-Isolated Patients.” Nature Medicine.
Brenner. 2021. Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths—Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action.” Nutrients.
Briggs, Goldstein, Kirwin, et al. 2021. Estimating (quality-adjusted) life-year losses associated with deaths: With application to COVID-19.” Health Economics.
Burridge, Fan, Jones, et al. 2021. Predictive and Retrospective Modelling of Airborne Infection Risk Using Monitored Carbon Dioxide.” Indoor and Built Environment.
Cevik, Kuppalli, Kindrachuk, et al. 2020. Virology, Transmission, and Pathogenesis of SARS-CoV-2.” BMJ.
Chang, Harding, Zachreson, et al. 2020. Modelling Transmission and Control of the COVID-19 Pandemic in Australia.” Nature Communications.
Cirillo, and Taleb. 2020. Tail Risk of Contagious Diseases.” Nature Physics.
Cuschieri, Calleja, Devleesschauwer, et al. 2021. Estimating the Direct Covid-19 Disability-Adjusted Life Years Impact on the Malta Population for the First Full Year.” BMC Public Health.
Dolan, and Kahneman. 2008. Interpretations Of Utility And Their Implications For The Valuation Of Health*.” The Economic Journal.
Entrenas Castillo, Entrenas Costa, Vaquero Barrios, et al. 2020. ‘Effect of Calcifediol Treatment and Best Available Therapy Versus Best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical Study’.” The Journal of Steroid Biochemistry and Molecular Biology.
Fais, Juskeviciene, Francardo, et al. 2022. Drug-Free Nasal Spray as a Barrier Against SARS-CoV-2 and Its Delta Variant: In Vitro Study of Safety and Efficacy in Human Nasal Airway Epithelia.” International Journal of Molecular Sciences.
Friedland, Tucker, Goodall, et al. 2022. In Vivo (Human) and in Vitro Inactivation of SARS-CoV-2 with 0.5% Povidone-Iodine Nasal Spray.” Australian Journal of Otolaryngology.
Fröba, Große, Setz, et al. 2021. Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta.” International Journal of Molecular Sciences.
Hall, and Viney. 2021. Quality Adjusted Life Years in the Time of COVID-19.” Australian Health Review.
Herbrich, Rastogi, and Vollgraf. 2020. CRISP: A Probabilistic Model for Individual-Level COVID-19 Infection Risk Estimation Based on Contact Data.”
Howard, Huang, Li, et al. 2021. An Evidence Review of Face Masks Against COVID-19.” Proceedings of the National Academy of Sciences.
Jarvis, and Kelley. 2021. Temporal Dynamics of Viral Load and False Negative Rate Influence the Levels of Testing Necessary to Combat COVID-19 Spread.” Scientific Reports.
Karlinsky, and Kobak. 2021. Tracking Excess Mortality Across Countries During the COVID-19 Pandemic with the World Mortality Dataset.” Edited by Miles P Davenport, Marc Lipsitch, Marc Lipsitch, Lone Simonsen, and Ayesha Mahmud. eLife.
Killingley, Mann, Kalinova, et al. 2022. Safety, Tolerability and Viral Kinetics During SARS-CoV-2 Human Challenge.”
Kimmitt, and Redway. 2016. Evaluation of the Potential for Virus Dispersal During Hand Drying: A Comparison of Three Methods.” Journal of Applied Microbiology.
Kozlov. 2022. Could a Nose Spray a Day Keep COVID Away? Nature.
Lescure, Bouadma, Nguyen, et al. 2020. Clinical and virological data of the first cases of COVID-19 in Europe: a case series.” The Lancet Infectious Diseases.
Lewis. 2021. COVID-19 Rarely Spreads Through Surfaces. So Why Are We Still Deep Cleaning? Nature.
Lewnard, Hong, Patel, et al. 2022. Clinical Outcomes Among Patients Infected with Omicron (B.1.1.529) SARS-CoV-2 Variant in Southern California.”
Miguel, and Mobarak. 2022. The Economics of the COVID-19 Pandemic in Poor Countries.” Annual Review of Economics.
Miles, Stedman, and Heald. 2020. Living with Covid-19: Balancing Costs Against Benefits in the Face of the Virus.” National Institute Economic Review.
Murai, Fernandes, Sales, et al. 2020. Effect of Vitamin D3 Supplementation Vs Placebo on Hospital Length of Stay in Patients with Severe COVID-19: A Multicenter, Double-Blind, Randomized Controlled Trial.” medRxiv.
———, et al. 2021. Effect of a Single High Dose of Vitamin D 3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.” JAMA.
Neve, Clark, Krekel, et al. 2020. Taking a Wellbeing Years Approach to Policy Choice.” BMJ.
Noakes, and Sleigh. 2009. Mathematical Models for Assessing the Role of Airflow on the Risk of Airborne Infection in Hospital Wards.” Journal of the Royal Society Interface.
Piroth, Cottenet, Mariet, et al. 2021. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study.” The Lancet Respiratory Medicine.
Quilty, Clifford, Hellewell, et al. 2021. Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study.” The Lancet Public Health.
Randall, Ewing, Marr, et al. 2021. How Did We Get Here: What Are Droplets and Aerosols and How Far Do They Go? A Historical Perspective on the Transmission of Respiratory Infectious Diseases.” Interface Focus.
Reddy. 2020. Population Health, Economics and Ethics in the Age of COVID-19.” BMJ Global Health.
Reis, Moreira-Silva, Silva, et al. 2022. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial.” The Lancet Global Health.
Robinson, Sullivan, and Shogren. 2021. Do the Benefits of COVID-19 Policies Exceed the Costs? Exploring Uncertainties in the Age–VSL Relationship.” Risk Analysis.
salman. 2021. A Double-Blinded, Placebo-Controlled Parallel, Phase 3 Clinical Efficacy Study Evaluating Nitric Oxide Nasal Spray (NONS) To Treat and Prevent the Exacerbation of Infection in Individuals With Documented Asymptomatic or Mild COVID-19.” Clinical trial registration NCT05012319.
Sanotize Research and Development corp. 2021. Multi-Center, Randomized, Controlled, Phase II Clinical Efficacy Study Evaluating Nitric Oxide Releasing Solution Treatment for the Prevention and Treatment of COVID-19 in Healthcare Workers and Individuals at Risk of Infection.” Clinical trial registration NCT04337918.
Spiegelhalter. 2020. Use of ‘Normal’ Risk to Improve Understanding of Dangers of Covid-19.” BMJ.
Stapelberg, Smoll, Randall, et al. 2021. A Discrete-Event, Simulated Social Agent-Based Network Transmission (DESSABNeT) Model for Communicable Diseases: Method and Validation Using SARS-CoV-2 Data in Three Large Australian Cities.” PLOS ONE.
Sze To, and Chao. 2010. Review and Comparison Between the Wells–Riley and Dose‐response Approaches to Risk Assessment of Infectious Respiratory Diseases.” Indoor Air.
University Hospital, Angers. 2021. COvid-19 and Vitamin D Supplementation: A Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-Risk COVID-19 Patients (CoVitTrial).” Clinical trial registration NCT04344041.
Wang, Chia C., Prather, Sznitman, et al. 2021. Airborne Transmission of Respiratory Viruses.” Science.
Wang, Wensi, Wang, Lai, et al. 2022. Evaluation of SARS-COV-2 Transmission and Infection in Airliner Cabins.” Indoor Air.
Weitz, Beckett, Coenen, et al. 2020. Modeling shield immunity to reduce COVID-19 epidemic spread.” Nature Medicine.
Winchester, John, Jabbar, et al. 2021. Clinical Efficacy of Nitric Oxide Nasal Spray (NONS) for the Treatment of Mild COVID-19 Infection.” The Journal of Infection.
Wong, Kelly, Ip, et al. 2013. Case Fatality Risk of Influenza A(H1N1pdm09): A Systematic Review.” Epidemiology (Cambridge, Mass.).
Wouterse, Ram, and van Baal. 2022. Quality-Adjusted Life-Years Lost Due to COVID-19 Mortality: Methods and Application for The Netherlands.” Value in Health.
Xie. 2020. A Novel Monte Carlo Simulation Procedure for Modelling COVID-19 Spread over Time.” Scientific Reports.
Zhao, Merchant, McNulty, et al. 2021. COVID-19: Short Term Prediction Model Using Daily Incidence Data.” PLOS ONE.