COVID-19 Prevention

1. Overview

1.1 Current Vaccines Cannot Solve COVID-19 Pandemic

The COVID-19 pandemic is affected by various factors.^[1] If only relying on vaccines, the war between humans and COVID-19 may become a long-term war of attrition, and human society will not be able to return to its previous normal state. According to the current vaccination rate, it will take 7 years for the world to return to its previous normal state.^[2]. This anticipation does not take into account the mutation of COVID-19. The Coronavirus is mutating in the direction of becoming more infectious^[3] and immune escape^[4], and it has greatly reduced the effectiveness of some original vaccines and even made some vaccines ineffective.^[5] Facing the recent South African variant, the effectiveness of the Oxford-AstraZeneca, Johnson & Johnson and Novavax vaccines are only 21.9%、57% 、49% respectively;^[6] The level of neutralizing antibodies induced by Moderna vaccine is only one-sixth of the previous level;^[7] Pfizer vaccine antibody protection was reduced by approximately two-thirds.^[8]

There are also two extremely important issues that are ignored by most people:

• The current COVID-19 vaccines are designed to prevent vaccinated person from getting sick, and it may not be possible to prevent the vaccinated person from being infected or spreading the virus.^{[9], [10], [11]}

• For some pathogens, when the vaccine cannot eradicate the pathogen, it will push the pathogen to evolve.^[12]

In January, science journal Nature surveyed more than 100 immunologists, infectious disease experts, and virologists. About 90 percent believed that COVID-19 could not be eradicated and would become a local epidemic, 71 percent thought that the most important factor was the immune escape of the virus.^[13]

1.2 Current Epidemic Prevention Measures

The current epidemic prevention measures can be summarized into two categories:：

Measurements outside body minimize the amount of virus entering the body, such as maintaining social distance, avoiding gatherings, ventilating, washing hands, disinfecting, wearing masks, wearing respirators (N95, PAPR, etc.), isolation and lockdown, etc.^[14]

Maintaining social distance (2 meters) can greatly reduce the risk of droplet transmission, and indoor ventilation can reduce aerosol transmission.

The best personal protective equipment is powered air purifying respirator (PAPR). Professional PAPR has a assigned protection factor of up to 1000 (APF, the reciprocal of the total inward leakage).^[15]

Measurements in vivo remove the virus in the body or suppress the replication of the virus as much as possible; such as natural immunity, vaccination, immunity enhancement, and the use of drugs.

The most ideal measurement in vivo is to develop a vaccine or drug that can completely eradicate the virus in the body (but at present, there is no such ideal vaccine or drug in the world). People should take various protective measures to minimize the risk of infection.

1.3 How to Control COVID-19 Epidemic

• Using innovative technologies to increase the protection index of individuals or groups to more than 500.

• Block the spread of the virus and prevent the virus from evolving.

2. Limitations of Current Epidemic Prevention Measures

2.1 Vaccines Are Not a Panacea

COVID-19 vaccines are divided into four categories, with hundreds of candidates.^[16]

Vaccines can slow or stop the epidemic spread, but there are limitations:^{[17], [18], [19], [20]}

1. Vaccines are unable to avoid illness 100%, clinical trial effective rate is 60%~95%,^[21] but the actual efficiency is still uncertain.^[19]

2. If the virus mutates to a certain degree,^{[3], [4]} vaccine efficiency is greatly reduced or even ineffective.^{[5], [6], [7], [8]}

3. To form herd immunity, ~90% of people need to be vaccinated in a short time.^[22]

4. The duration of the antibody is more than a few months, but it varies from person to person.^[23]

5. Usually vaccine development takes about 10 years, the COVID-19 vaccines are approved by emergency use, and the safety of the vaccine still needs time to verify.^[11]

For RNA viruses that are easily mutated, herd immunity is difficult to succeed:

1. Research by US CDC shows that the effectiveness of influenza vaccines is usually 40-60%, but some have an effectiveness of only 23%.^[24]

2. The antibodies after natural infection with SARS-CoV-2 only last a few months.^{[25], [26], [27]}

3. About 76% of the population in Manaus, the capital of Brazil's Amazonian state, was infected with SARS-CoV-2 to produce antibodies, but the second epidemic still broke out.^[28]

4. The cases of positive retest COVID-19 patients indicated that a small number of COVID-19 patients would carry the virus in their body after recovery. The virus mainly remains in the digestive tract and may be released intermittently.^{[29], [30]}

2.2 Limitations of COVID-19 Vaccines

2.2.1 Vaccines Prevent Illness, But Not Infection

The current COVID-19 vaccines are to prevent the vaccinated person from getting sick, but it may not necessarily prevent the vaccinated person from being infected or becoming an asymptomatic spreader.^{[9], [10], [11]}The medias reported that the effectiveness of the COVID-19 vaccines is 60%-95%, which refers to effective immunity, not sterilizing immunity. Effective immunity can prevent illness but still cause asymptomatic infection, while sterilizing immunity can eradicate the virus and prevent the vaccinated person from being infected.^{[31], [32]} There is currently no evidence that any COVID-19 vaccine can produce sterilizing immunity.^[33] Sterilizing immunity is the ultimate goal of vaccine development.

If a COVID-19 vaccine only prevents illness but not infection, then people who are infected but not sick after being vaccinated may become asymptomatic spreaders of the virus. If a country has popularized vaccines, but the people no longer take protection, the confirmed cases will drop significantly, but the actual infection rate will continue to increase. When the antibody concentration is reduced to a certain level, or the variant can escape immunity, it is prone to a second round of epidemic outbreaks. In addition, herd immunity may not be effective in epidemic areas, and those who have not been vaccinated are more likely to be infected by the virus carried by the vaccinated. Therefore, vaccinated people still need to wear masks.

2.2.2 Vaccines Are Pushing Pathogens to Evolve

Andrew Read, a virologist at the University of Pennsylvania in the United States, warned that low-efficacy vaccines could even promote the development of more dangerous virus strains.^[34]

A vaccine is a novel selection pressure placed on pathogens. If the vaccine cannot completely eradicate the pathogens, then the remaining pathogens with the greatest fitness, those able to survive, somehow, in an immunized world, will become more common.^[12] Not only vaccines, some other measures, such as treatment, will also bring selective pressure on the virus and drive its evolution.^[35] The consequences of various protective or therapeutic measures should be considered to avoid virus evolution as much as possible.

2.3 High Cost of Quarantine And Lockdown

Quarantine and lockdown are very effective in a small area or within a short period of time, but they also have limitations:

1. For the asymptomatic and patients with a long incubation period, quarantine cannot completely block the virus spread.

2. The virus spread through surfaces reduces the quarantine effect.

3. Once the virus spreads through animals on a large scale, it is difficult to eradicate the virus.^[36]

At present, the proportion of asymptomatic infections of COVID-19 exceeds 80%.^[37] It is difficult to prevent. When the virus breaks through the quarantine and enters the general population, it will spread rapidly. The economic and social costs of quarantine and lockdown are very high.

2.4 Aerosol Transmission of SARS-CoV-2

There are three modes of SARS-CoV-2 transmission: droplets, contact and aerosols.^[38]

In poorly ventilated enclosed spaces, such as airplanes, high-speed rails, subways, taxis, buses, wards, dormitories, apartments, elevators, toilets, office buildings, shopping malls, supermarkets, cinemas, restaurants, etc., SARS-CoV-2 can spread through aerosols.

The China CDC's paper lists a lot of evidence of the aerosol transmission of SARS-CoV-2.^[39] The distances transmitted by aerosols and droplets are different during exhaling, coughing and sneezing.^[40] Most of human social activities are carried out indoors, so understanding aerosol transmission is very important for epidemic prevention.

The study found that the half-life of SARS-CoV-2 in aerosols are 1.1 to 1.2 hours, and the half-lives on the surface of stainless steel, plastic and cardboard are 5.6, 6.8 and 3.5 hours, respectively.^[41] Ultraviolet (UV), temperature and humidity will affect the half-life of SARS-CoV-2, and it can be calculated that the half-life under normal temperature and low humidity is 10 times greater than that of high temperature and high humidity.^[42] If one million viruses were placed on various surfaces, it would require 20 half lives to become undetectable and non-infectious.^[43]

Aerosol transmission is more difficult to prevent than droplet and contact transmission, because aerosol particles are small and can stay in the air for a long time; and it is easy to penetrate ordinary masks that do not contain meltblown non-woven fabric (cotton masks, gauze masks, paper masks, etc. ).

2.5 Surgical Mask and Hand Washing

The date in the clinical trials on use of respiratory protection (see the following table) suggest that in homes or student dormitories, surgical masks and hand-washing do not seem to be very effective in preventing influenza, and sometimes the infection rate is about the same as without any protection.^[44] The main reason should be that in the indoor space, the virus spread is dominated by aerosol transmission. Surgical masks and hand washing are effective in reducing droplet transmission and contact transmission of the virus, but their effectiveness in preventing aerosol transmission is very limited.

Milton’s experiment in 2013 discovered that among particles exhaled by influenza patients, fine particles (≤5 µm) contained 8.8 fold more viral copies than did coarse particles (>5 µm). Surgical masks reduced viral copy numbers in the fine fraction by 2.8 fold and in the coarse fraction by 25 fold.^[45] This experiment also shows that the exhalation leakage of surgical masks is about 33%, while the inhalation leakage of surgical masks we tested is 30%-40%. It can be believed that the exhalation leakage and inhalation leakages are approximately equal, which means that the protection index of surgical masks is equal to the exhalation protection factor (2-3).

2.6 Actual Protective Performance of N95/KN95 Respirators

The above table also shows that if healthcare workers can’t keep wearing masks, there is no significant difference in protection effect between surgical masks and N95, even the same as without a mask.^[44] Only by strictly keeping wearing masks can there be a good protective effect. Among more than 20,000 healthcare workers at Beaumont Health reporting direct exposure to a COVID-19 positive individual, those wearing an N95/PAPR mask had a significantly lower seropositivity rate (10.2%) compared to surgical/other masks (13.1%) or no mask (17.5%).^[46]

If all people wear surgical masks, the herd protection index is less than 9, which is far from enough to avoid infection in high-risk places. Germany weighs up mandatory FFP2 masks in shops and on transport.^[47] Czech government is considering making it mandatory to wear respirators in shops and public transport.^[48]

In fact, N95/KN95 respirators are not suitable for all people, and children, the elderly and heavy physical workers are not recommend to wear N95/KN95 respirators.^[49] Because breathing resistance of N95/KN95 respirator is usually much larger than that of a surgical mask, it will cause the wearer to unconsciously or actively increase leakage to reduce resistance, and it is not recommended to wear N95/KN95 for a long time, otherwise it will cause lung damage^[50] and headache.^[51]

Although N95/KN95 respirator requires a assigned protection factor of more than 10^[52], and medical N95 respirator requires a fit factor of at least 100; it usually need to pass a fit test to achieve a good protective effect.^[53] In actual wear, the face shape and the quality of the mask have a great influence, and the fit factor of most N95/KN95 masks ranges from 5-20.^[54] The same N95/KN95 masks are worn by the general population, and the fit factors vary greatly. Only fit factors from a few people can reach 100 or more, and those from some people are below 10.^{[55], [56]}

The US CDC does not recommend ordinary people to wear masks with breathing valves, transparent masks and transparent face shields (cannot prevent aerosol transmission).^[57]

2.7 Protective Performance of Double Masks

The US CDC recently recommended double masks on its official website. The researcher reported that when infected and healthy people all wearing two masks (surgical masks + cotton masks), aerosol transmission could be reduced by 96.4%.^[58]

The double masks in the study have a herd protection index of 30, but increase breathing resistance. The HPI of this kind of double mask is still far from those used to block the aerosol transmission of SARS-CoV-2.

It should be considered that some double-mask modes would be counterproductive. Our research has discovered that when one of the double masks is N95 with a fit factor of above 100, which is worn over a surgical mask, it is very likely that the protective performance will be worse than wearing only one N95 mask.

3. Infection Risk Assessment of COVID-19

3.1 Infective Dose

Infective dose is the quantity of a pathogen that is necessary to cause infection in a susceptible host. Different bacteria or viruses have very different infective doses; the infective dose for the influenza A variant, Influenza A2, is greater than 790 organisms via the nasopharyngeal route.^[59]

The infectious dose of SARS-CoV-2 is not yet known, and some researchers speculate that the infectious dose of SARS-CoV-2 is about 300.^[60] The more viruses people are exposed to, the risk of infection and developing serious illness would be higher.^[61]

3.2 Viral Load

Viral Load is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens.^[62] A patient’s high viral load increases the risk of infection in contacts.^[63]

The viral load in the saliva of COVID-19 patients is high, with an average of about 10⁵~10⁷ copies/mL^{[64], [65]} Thousands of viruses may be released in a single cough.^[66] The aerosol particles produced by talking are several times that of breathing, and talking loudly will be more than ten times.^{[67], [68]} The viral load of asymptomatic and symptomatic patients with COVID-19 is similar, and the transmission of asymptomatic patients may be a key factor in community transmission.^[69] In the super-spreading event that occurred in Tonghua City, Jilin Province in January 2021, the super-spreader was a salesman, and it has caused at least 141 related cases of infection. The salesman hosted product promotion training courses, and the COVID-19 infection rate of the participants in the three courses were 90%, 90% and 38% respectively.^[70]

Schools need to prevent the occurrence of super-spreading events, and the teachers should pay more attention to protecting themselves. One reason is that teachers have contact with many students, the other reason is that once an epidemic breaks out, dormitories and classrooms are high-risk places, and the third reason is that lectures are more likely to spread the virus than breathing.

Yang et al. collected aerosol samples during the 2009–2010 flu season in a health centre, a day-care facility and onboard airplanes. The total virus concentrations in half of the samples ranged from 5800 to 37 000 copies/m³. On average, 64 percent of the viral genome copies were associated with fine particles smaller than 2.5 µm, which can remain suspended for hours. Modelling of virus concentrations indoors suggested a viral emission rate of 1.6 ± 1.2 × 10⁵ genome copies m⁻³ air h⁻¹ and a deposition flux onto surfaces of 13 ± 7 genome copies m⁻² h⁻¹ .^[71]

A research conducted by Maosheng Yao’s team at Peking University and Beijing Chaoyang CDC revealed that the estimated viral emission rate from some COVID-19 patient ranged from 1.03 × 10⁵ to 2.25 × 10⁷ viruses h^-1, and in some environmental samples, such as a sample from the air of an unventilated quarantine hotel toilet room, the SARS-CoV-2 concentration is as high as 6000 viruses m⁻³.^[72]

3.3 Estimation of Virus Concentration in High-Risk Locations

Assuming that there is only one COVID-19 patient in a high-risk location, the SARS-CoV-2 emission rate is 6 million per hour. The virus concentrations at 1, 10, and 60 minutes are estimated respectively when the patient is unprotected and the environment is not ventilated.

The above table shows that in high-risk places with volumes below 1000 m³, if the ventilation is poor, the virus concentration can easily reach 3000 to 60000/m³, and the virus concentrations in some small enclosed places can even reach 1 million/m³. Accurate estimation should take into account the air exchange rate (AERs) and the half-life of the virus in the aerosol. When only AERs are considered, the actual virus concentration can be simplified as the viral emission rate divided by the volume and AERs. Typical AERs are 13 ACH in hospitals, 9 ACH in schools and 4 ACH in commercial offices in USA (ACH, air changes per hour).^[71]

The above table only estimates the virus concentration based on normal breathing. If an infected person coughs, more viruses will be released. A severely infected person who's coughing frequently can fill a poorly ventilated room with as many as 7.4 million copies of the coronavirus for every cubic meter of air, according to researchers Michael Riediker and Dai-Hua Tsai. These findings implicated that individuals may be at risk of infection if they spend more than a few minutes in such a small room.^[73] In addition, the virus concentration is related to the infection rate in the area. At 10% infection rate, the virus concentration in high-risk places may be much higher than that at 0.1% infection rate. So as the epidemic spreads, people are more likely to be infected.

3.4 Terms

Commonly used terms of personal protective equipment:

Filtration Efficiency: usually refers to the filtration efficiency of a filter for ~0.3 µm particles under a certain flow rate.

Total Inward Leakage (TIL): the ratio of the breathing-zone concentration of pollutants to the external concentration after using a respirator.

Assigned Protection Factor (APF): APF is the decrease of the concentration of harmful substances in the inhaled air if a respirator is used properly. APF is the inverse of the total leakage rate of the respirator.

Fit Factor (FF): FF is the reciprocal of face seal leakage (FSL), which is calculated by TIL minus filter penetration.

In order to facilitate the discussion, the following terms are defined.

Exhalation Protection Factor (EPF): the decrease of virus concentration in exhaled air after using a respirator.

Personal Protection Index (PPI): It is the decrease of the concentration of harmful substances in the inhaled air when an individual uses a respirator. PPI reflects the actual protection performance, not necessarily the same as APF, but also related to breathing volume and the external environment.

Herd Protection Index (HPI): the decrease of the concentration of viruses in the inhaled air when all people wear a certain type of respirator. HPI is usually the product of PPI and EPF

3.5 Infection Risk Assessment

In a certain period of time, when inhaled virus number (Nv) is above the infectious dose, an individual may be infected. The following is the formula for calculating inhaled virus number, which is directly proportional to the virus concentration, tidal volume and time, and inversely proportional to the protection index:

Nv = Virus Concentration X Tidal Volume X Time / Protection Index

The long-term tidal volume of Chinese residents is 15.7 m³/d, and the short-term tidal volume under resting, sitting, light activity, moderate physical activity, heavy physical activity, and very heavy physical activity are 5.5, 6.6, 8.2, 21.9, 32.9, and 54.8 L/min, respectively.^[74]

Assuming that an individual's tidal volume is 0.5 m³/h, the initial virus concentration is estimated to be 3000 or 60000 copies/m³, and the infective dose is 300 or 1000. The minimum times required for infection (Ti) are estimated and listed in the table below when wearing different respirators. The initial virus concentration refers to the virus concentration when the infected person does not take any protection. When Ti is longer than a certain time, such as 8 hours, the time is enough for the immune system to eliminate the inhaled viruses, and it can be considered that the infection will not happen.