Information sources

Introduction
This book provides an overview of the many topics within coronavirus SARS-CoV-2 transmission and non-pharmaceutical, do-it-yourself prevention methods. I wrote it for health professionals and the public who want a summary of each topic, with links to over a thousand publications with in-depth details. If you need to work on a coronavirus-related task you have not worked on before, or need more information on a topic you already know somewhat, or are going into a risky transmission situation, or need to explain those topics to someone, then you are one of the people I designed this book for.
When someone needs to start learning about a topic, they often first look at secondary sources like this, to understand the overall pattern. Then the secondary source refers them to primary sources. This takes less time than searching the internet and medical databases to start with many primary sources, getting lost in the details several times, then finally understanding, and then beginning to do useful work. Managers, experts, and the public often change tasks, sometimes with only a short time to prepare. They need to save time in learning the information and starting the project, by preventing misunderstandings which lead to dead ends and wasted work. People could start learning another topic by searching for primary sources. But researchers published hundreds of thousands of articles on SARS-CoV-2. Someone starting to read this could get lost and confused, like the cliché about not seeing the forest for the trees. A secondary source serves as a map of the forest, showing where the different kinds of trees are, and the relationships between them.
Many SARS-CoV-2 publications differ or disagree with each other. Someone reading them could feel confused by the controversies and competing opinions. I tried to assemble a neutral or middle way synthesis summarizing the hypotheses on each topic, that is accurate enough for the reader to take action.

For over forty years I worked on several infectious disease and malnutrition prevention projects in different cultures. Each time I started on a topic or with people I knew little about, I used secondary sources to see an overview, and learned more details. I used several of those books as models for this book. The Control of Communicable Diseases Manual (CCDM) (1) (Heymann) summarizes the microbiology, transmission, pathology, prevention, and treatment of many diseases, in one to fifteen pages per disease. When health professionals need to work on another infectious disease program, they often read the relevant chapter of this book. Even if they worked with that topic several times, they reread the chapter each time. When I started working in a malaria program, I read Essential Malariology by Bruce-Chwatt, and continued working by reading parts of the later editions edited by Warrell and Gilles. When I started working on malnutrition projects, I read Malnutrition by Robson. As that book went out of date, I used the Handbook of Nutrition and Food (Berdanier, Dwyer, & Heber) which has even more topics on normal nutrition. Using those books saved much time and wasted effort in working with people, writing reports, and improving programs.

Since the authors published those books on paper, nowadays people developed web links in electronic publications. So, for this ebook and web pages I added links in the citations and references, so the reader can study my summary of each topic, and then click to look at each publication I cited. The print version has the URL web addresses in the references, which readers can type into their computers.

This book started as web pages on the site of the School of Public Health of San Diego State University, in California, USA, where I teach sometimes. As the SARS-CoV-2 coronavirus pandemic was starting, people kept calling and e-mailing me, asking questions about this new disease. I often looked at the new research coming out daily in science journals, and wrote summaries, and sent them to people. I asked the School of Public Health what I should do about this, and they asked me to post it on their web site. At first, it was only 12 pages long, with 68 references. I continued adding more information, and after almost three years, it had 96 text pages with over a thousand references.

Topics
This book summarizes information on SARS-CoV-2 transmission routes and non-pharmaceutical prevention methods, for readers to use themselves, and to explain that to others, to prevent getting COVID-19.
It has little on these other useful topics:
Medical treatments
Pathology, except having some on how SARS-CoV-2 enters some kinds of cells and organs, gets into body fluids, and spreads to other people
Noscomial infections in health care facilities
Vaccines and immunization
Mutating variant viruses
Rapid antigen tests and self-testing
Origins of SARS-CoV-2
Epidemiology news, such as increasing cases in one area, then decreasing
Epidemiology statistics, such as R0, incidence, epidemic curves, predicted projections, demographic statistics, and disparities
Government ordered interventions or mandates such as travel bans, lockdowns, or contact tracing, except when they discovered more about SARS-CoV-2 transmission and individual prevention
Other diseases, except some that studied transmission and prevention methods for influenza and SARS-CoV-2, and some comparing the characteristics of SAR-CoV-1 and SARS-CoV-2

Information Sources

[Date of latest publication cited: October 31, 2023]

Since the start of the pandemic, scientists published hundreds of thousands of articles on SARS-CoV-2. For example, by September 29, 2023 the World Health Organization recorded 728,037 publications on COVID-19 (WHO COVID-19 Research Database). Among the topics summarized in this book, there were the following numbers of publications:  27,462 on SARS-CoV-2; 1,293 on Angiotensin-Converting Enzyme 2; 1,205 on masks; 1,142 on personal protective equipment; and 785 on physical distancing. Since the pandemic started, Thousands of researchers studied many aspects of the new virus, and many organizations published their information on these topics in three types of formats:

So this web page meets the needs of people who want a synopsis of discoveries on COVID-19 transmission and prevention, in one location, in plain English, with links and references to the many research articles supporting each statement.  Most people’s information needs are satisfied by the news reports and public health recommendations.  But many health professionals, researchers, interested people, and leaders of organizations and groups would want this web page’s “one stop shopping” summary with links to each scientific article explaining the reasons for the recommendations.

It is not possible for one or a small number of people to read and summarize all of those. So, I needed to take representative samples from each of many subtopics, research methods, authors, viewpoints, and search methods. I tried to sample these according to the numbers of each kind, to balance them, analogous to the statistical sampling method Probability Proportional to Size (PPS). I chose which publication to include or exclude according to the list of topics above, so it is like a curated selection.

I chose mostly peer-reviewed articles in scientific journals, and some health news articles. I searched in these databases and web sites: PubMed, LitCOVID, PLOS COVID-19 Updates, F1000 Research, BMJ’s Coronavirus (covid-19) Hub, the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC); SpringerNature’s Coronavirus (COVID-19) Research Highlights, and New England Journal of Medicine Coronavirus (Covid-19). I often looked in journals which had many articles on these topics: The Lancet; Clinical infectious Diseases; Journal of the American Medical Association (JAMA); and Annals of Internal Medicine. I also looked in these health newsletters: STAT News; Medical Xpress, Center for Infectious Disease Research and Policy (CIDRAP); Medical News Today; MedPage Today; ACCESS Health International, Tulane Outbreak Daily (Miller C) (now “The Transmission” from the Global Center for Health Security) (Miller C); The Conversation; and Nature News. Those health news journalists recommended useful science journal articles, which I summarized in this book. The science journal articles had accurate information, but often refrained from discussing broad implications. The health news articles tended to explain the broader implications more than journal articles did, so I often summarized and cited both.

I searched PubMed for peer-reviewed or good quality articles specifically on transmission routes of coronavirus disease COVID-19, using the search terms “SARS-CoV-2”, “coronavirus”, “COVID-19”, “2019-nCoV”, “transmission”, “saliva”, “mucous”, “blood”, “feces”, “fecal”, “fomite”, “surface”, “droplet”, “aerosol”, “asymptomatic”, “pregnancy”, “birth”, “childbirth”, “dog”, “cat”, “sexual transmission”, “vagina”, “testes”, “semen”, and “food”.  I included original research studies of the community transmission routes of COVID-19 infected people.  I included articles published in English, and some translated from Chinese.

I chose mostly publications people can view for free on the internet, especially Open Access journal articles.  I also chose some articles from subscription news sites that made their coronavirus articles viewable for free.  I chose some articles one needs to pay to view.  Some journals published some research articles behind a paywall, but also on US National Library of Medicine PubMed Central (PMC) for free.  So, in the reference I listed all the URL web addresses the article is posted on, and in the citation I linked it to the freely available post location.

When SARS-CoV-2 began to spread, scientists imagined several hypotheses for each aspect of transmission and prevention, and then conducted experiments testing each hypothesis.  By the second or third year, most scientists agreed on a consensus for most topics.  In the first year, I tried to include evidence and arguments for each alternative hypothesis, and later added explanations about why scientists later commonly accepted one, to show the range of ideas.  For example, at first scientists studied transmission by many bodily fluids via air, surfaces, and direct contact.  Later, most agreed that saliva and mucous spread as aerosols and droplets through indoor air probably transmitted SARS-CoV-2 to most people who had COVID-19.  For another example, scientists found that several chemicals in mouthwashes destroy SARS-CoV-2.  But, even if someone frequently gargled those mouthwashes, viruses could still float through their nose and mouth into their respiratory system and infect the mouthwash user.  I included information on the other transmission modes, and mouthwashes, and cited and linked to those articles, so readers can assess the many hypotheses themselves.

Unlike many review articles, I did not rate the quality of research methods.  If an article used mostly valid methods, and had useful information, then I included it.  I briefly described the research methods, and linked to the publication, so readers could understand how the authors discovered that information.  Many reviews of literature count numbers of references on each subtopic, or supporting each hypothesis, or using each research method.  But I did not do that; I mainly wrote about practical information to understand transmission and prevention.

I tried to use the main ideas of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement (Page MJ, McKenzie PLOS; Page MJ, McKenzie BMJ), as described in the paragraphs above.  I looked at potential biases of each article’s research methods, and then explained those in each chapter of this book.  For example, I often stated whether a research project cultured virions in cells (which shows the viruses were currently viable in that sample) or used polymerase chain reaction (PCR) (which shows positive for either currently or previously viable viruses).  But I did not record the reasons why I included or excluded each article, in order to save time.  In 2020 – 2021, I often looked at over 20 new articles per day, and added up to five per day to the web page.  Review authors should use PRISMA for most health science situations.  But in a rapidly changing crisis with a wide range of related topics, in which researchers published hundreds of thousands of articles, and thousands of people were dying per day, using PRISMA would have slowed my work.  Instead, I often found and added the new articles’ information to the web site within hours or days after the journal or web site published it.  To do this, I used the sampling method similar to Probability Proportional to Size (PPS) described above.

Studies using PRISMA typically review a narrower topic range than I did.  In most, their searches returned hundreds of papers, and then included tens of them.  One of the largest studies using PRISMA that I cited (on SARS-CoV-2 infection in pregnancy) searched and returned 3,234 papers, then included 204 (Sturrock).  If some people attempted to use PRISMA for the topics I did, they would probably need several researchers working thousands of person-hours, and a large budget.

While adding hundreds of references, I deleted some references which later research found were too simple or partly incorrect.  In 2020, I added some new research articles posted on the preprint servers MedRxiv and BioRxiv, in order to help readers find those new discoveries.  I looked at those again months later; if a peer-reviewed journal published them, I changed the citation and reference to the journal article.  If no journal published the preprint article, then I deleted it from the web pages.  I kept some of the earliest explanations of transmission or prevention that showed step-by-step reasoning to the correct conclusion using the limited information available then, even though they appeared in blog posts or other not-very-scientific publications, especially those by Bromage, Burch, and Kay.

In writing explanations, did not just say that a transmission route could or could not occur, but instead said that it more or less probably occurred.  I did not write that an action could expose or not expose a person to SARS-CoV-2, but increased or reduced probability of exposure and transmission.  I did not write that a prevention method worked or did not work, but instead said that it decreased probability of transmission, or which method decreased probability more than another method.  My thinking on this comes from knowing that this view is literally biologically true, that probability is usually not a binary variable but is a continuous variable.

It also comes from years of discussing infectious disease prevention methods with a variety of Cambodian, Lao, Thai, and US peoples in challenging situations that made it difficult to do prevention methods.  For example, farmers doing low-tech physical labor in heat, usually recover by sleeping in a cool or less hot place at night.  If they slept in a mosquito net, they would continue feeling warm, might not sleep well and not recover enough to get up the next morning and work in the hot sun again.  So, they often balance their risks and stresses.  When the night is hot and they see no mosquitoes, they often sleep without the net.  When they see mosquitoes, they risk getting malaria, so sleeping warm in a net is worth feeling tired, because it decreases probability of getting malaria, wasting workdays while sick, and spending money on medicines.  When they feel hot and see a few mosquitoes, then they need to estimate which risk is worse, the heat or malaria.

This web site emphasizes selecting studies that each focused on one or a few variables, and held the other variables constant, because they actually can control the variables and participants, and obtain clear results. These are sometimes called mechanistic or laboratory studies. After researchers did several studies like that, and understood the situation, then they could do larger studies.  These had more variables, personnel, and participants, such as randomized controlled trials (RCT) or systematic reviews, with inferential statistics, sometimes called probabilistic studies.  I also included some articles and books with larger studies.

The weakness or disadvantage of mechanistic or laboratory studies is they show those processes occurring in controlled situations. But these may or may not occur as clearly in real life. So, scientists take the discoveries made in mechanistic or laboratory studies and test them in probabilistic community studies and randomized control trials. But, the weakness of many of these larger, complex studies is they can only partially regulate the variables, personnel, and participants, especially if the personnel and participants are sometimes away from the researchers’ supervision.  If some control participants actually use the intervention sometimes, and some intervention participants actually do not use the intervention sometimes, this blurs the distinction between the two groups, and creates a bias for no statistically significant difference, and the null hypothesis.  The participants heard the instructions from the researchers, and also contrary ideas from other people.  So, RCTs could be a gold standard, but many studies cannot actually attain that high standard, and end inconclusive or statistically insignificant (Cash-Goldwasser et al.; Fischhoff et al.; Oliver et al.).

From my experiences managing field surveys and reading about clinical trials, it is difficult to follow up every participant and make sure they are doing what they are supposed to do.  When researchers did clinical trials following up each patient in obsessive detail, the trial could succeed in discovering the effects of the pharmaceutical tested.

For all those reasons, I chose to emphasize small mechanistic or laboratory studies that studied one or a few variables, and actually implemented the methods.  Most of these small studies used tangible, concrete methods that other people can easily understand and explain to more people so they understand.  Most of the hundreds of studies cited in this book were not gold standard, but a realistic standard, with two meanings of the word “realistic.”  1) They could do the research project according to feasible protocols.  2) they pay more attention to physical, tangible things than abstract ideas and complex mathematics.

These realistic studies each looked at a hypothesized sequence of cause and effect, and tested one or a few steps in the sequence to see if they actually happened. A study of one variable holds several other variables constant, and tests one variable at a time.  If many studies showed that each step could happen, then that showed that the whole sequence could happen.

A hypothesized transmission route is a cause and effect sequence.  Likewise, a proposed prevention method is a cause and effect sequence.  If researchers test each step, and they all happen, then that shows the whole transmission route probably happens, or the prevention method probably works.  If some steps do not happen, then that shows that step is preventing the whole sequence from happening.

Many sections of this web site look at one hypothesized cause and effect sequence, and summarize the studies on each step, and provide URL web links to the studies’ publications.  For example, in the chapter on Bodily Fluids, in the sections on Saliva and Mucous Droplets and on Aerosols, and the chapter on Human Organs, in the section Nose, the research studies cited show that each step can happen, and that aerosol transmission occurs.  In contrast, in the chapter on Bodily Fluids, in the section on Feces, and the chapter on Human Organs, section on Stomach, the studies show that that most steps of a hypothesized fecal-oral transmission route could happen.  But passing through the stomach into the intestines probably rarely happens, because gastric acid usually destroys SARS-CoV-2.  When the stomach is full of bland food, or when the person takes proton pump inhibiter medicines (PPI), and the acid changes to be more neutral, then SARS-CoV-2 could sometimes pass through the stomach and infect the intestines.

This web site emphasizes dividing each step and looking at each separately.  In contrast, randomized controlled trials and meta-analyses of them emphasize putting many variables into a research study, and testing the whole sequence.  If a step infrequently happened, then the studies show statistically insignificant results. It is especially difficult for large randomized control trials in communities or workplaces to monitor and regulate the variables, because they cannot enforce what every participant is doing all the time.

This comparison of mechanistic, laboratory, community, and randomized control trial studies is relevant to the later sections of this book. I included small, simpler studies, and larger, complicated, flawed, controversial studies that showed information useful for preventing SARS-CoV-2 transmission.