Wild Animal Source of COVID-19

According to various reports, the initial source of infection is believed to be wild animals, possibly the Chinese bat, Rhinolophus sinicus. ^{Reference Li, Yang and Ren7} In an interview, academician Zhong Nanshan also mentioned that wild animals, such as bamboo rats and badgers, may also be possible sources. Although there is no correlation between the initial case (December 1, 2019) and the follow-up cases (December 10, 2019), it may be arbitrary to exclude the first patient from the seafood market.^{Reference Cohen8} It could take more than 20 days to trace the patient’s contact history in the study; also, the patient’s forgetting or loss of personal contact history is reasonable. Of course, the data also suggest that COVID-19 may have originated far earlier than the time of that patient emerging. The analysis of 27 available genomes of the virus shows that they had a “recent common ancestor” as early as October 1, 2019. It is possible that the first infection case occurred far earlier before December 2019. The virus could have spread among people in Wuhan and other places quietly, and then concentrated and was detected in the seafood market; the virus may have been spreading within the population, and the seafood market may not have been the geographic source.^{Reference Kraemer9,Reference Andersen10}

However, the route of transmission to humans at the start of this event remains unclear. Bats are rare in markets in China but are hunted and sold directly to restaurants for food. The current most likely hypothesis is that an intermediary host animal has played an important role in the transmission from animal to human.^{Reference Cohen8}

Patients With Obvious Symptoms as Source of Infection

At present, the existing data and the actual phenomenon of infections showed that COVID-19 patients were the most important source of spread of infection, who could cause human-to-human transmission.^{Reference Phan, Nguyen and Luong11,Reference Chan, Yuan and Kok12} When the SARS-CoV-2 infection occurred, it may have been contagious before the appearance of symptoms. However, in SARS-CoV infection, it was reported that the more obvious symptoms were accompanied by a higher viral load, as well as stronger infectivity.^{Reference Yang, Wang and Li13} Whether COVID-19 has the same characteristic needs further investigation. Of course, this characteristic also needs close attention in prevention and control. Recent results showed that SARS-CoV-2 persists longer with a higher viral load and peaks later in the respiratory tissue of patients with severe disease; this phenomenon highlights the need for the prevention and control of the epidemic.^{Reference Zheng, Fan and Yu14} Unlike SARS, patients with COVID-19 had the highest viral load near onset of symptom, which could account for the fast-spreading nature of this epidemic.^{Reference To, Tsang and Leung15}

Patients Without Obvious Symptoms or in the Incubation Period

Some experts commented that people with mild or asymptomatic SARS-CoV-2 infection were not identified by epidemic prevention measures, thus accelerating the spread of the disease.^{Reference Wang, Horby and Hayden16} According to published research results, the average interval from onset to the first medical visit was approximately 5–6 days (5.8 days, 95% CI: 4.3–7.5; and 4.6 days, 95% CI: 4.1–5.1), which is similar to the estimated incubation period (the average incubation period of 10 confirmed cases is estimated to be 5.2 days (95% CI: 4.1–7.0).^{Reference Li, Guan and Wu3} During that time, although there were mild or no symptoms, the disease could be contagious. This finding highlights the importance of contact history tracing and maintained isolation of patients, suspected patients, and those with whom they have come in contact. This feature of COVID-19 is significantly different from that of the SARS-CoV infection outbreak in 2003. It is reported that SARS had no evidence of an incubation period and no shedding of virus.^{Reference Yang, Wang and Li13}

Asymptomatic patients were reported often, and this meant that there may be so-called “recessive infection cases” or asymptomatic infections.^{Reference Rothe, Schunk and Sothmann17,Reference Wei, Li and Chiew18} Most of the so-called “recessive infection cases” or asymptomatic infected people would eventually have symptoms and become ill.

Super Spreader

To date, no super spreader of the SARS-CoV-2 infection has been observed, but experts still warned people to pay attention to the possibility of super transmission events. Clustering cases were reported, but in limited scale.^{Reference Phan, Nguyen and Luong11,Reference Chan, Yuan and Kok12} These studies reported that a super spreader at a group gathering could cause 5–6 new cases of infection, with a maximum of 7 people newly infected being reported. However, compared with SARS-CoV infection, there were fewer clustered cases of SARS-CoV-2 infection and fewer cases compared with Middle East respiratory syndrome coronavirus (MERS-CoV) infection.^{Reference Hui19} However, other data showed that the transmission ability of COVID-19, with an R₀ = 2.2 to 2.68, indicates that there may be super spreaders of the virus.^{Reference Li, Guan and Wu3,Reference Wu, Leung and Leung20} For effective prevention of mass transmission, more must be learned about super spreaders of COVID-19.

Nearby Droplet Propagation

Inhalation of droplets containing virus particles exhaled by infected persons is the main mode of transmission of COVID-19, and the most common route of infection. This mode of transmission is very similar to that of the SARS-CoV infection. This transmission is easy to achieve during daily contacts, such as close family contact, by public transportation, in medical institutions, and so on. The reported COVID-19 cluster events may be explained by close family contact.^{Reference Li, Guan and Wu3,Reference Phan, Nguyen and Luong11,Reference Chan, Yuan and Kok12} It is generally believed that large size droplets play important roles in SARS spread, especially droplets with sizes of 5 μm-10 μm; so how about COVID-19? Because the symptoms of COVID-19 are very similar to those of influenza or the common cold, they are easily misdiagnosed in the early stages of infection by clinicians, other medical staff, or rescue personnel. In the early stages of infection, cutting off the spread of droplets may play an important role in the control of COVID-19 spread.

During the epidemic of SARS, aerosol transmission was 1 way of transmission, which was highly suspected to be 1 of the important transmission routes of outbreaks in hospitals and communities in severely affected epidemic areas. The epidemiological point here is that susceptible persons can be infected by inhalation of aerosols containing SARS-CoV without coming into contact with SARS-infected patients. Although the data of SARS cases were analyzed by epidemiological models, the results showed that the spread of SARS infection was not supported by aerosols, but by droplets. Officers of WHO believed that the possibility of SARS transmission through aerosols is very low. However, the propagation speed of COVID-19 is so fast, whether it is related to aerosol propagation needs further confirmation. However, the respiratory transmission will be greatly reduced by various protective measures, such as wearing face masks and isolation clothing.

Close Contact Transmission

Through direct or indirect contact with the patient’s secretions or body fluids, excreta, and other contaminated items, or working for, living with, treating, or visiting the patient, etc., pathogens may invade the body through the mouth, nose, and eye mucosa, to achieve transmission. During the epidemic period of SARS, close contact is another important way of transmission. Whether COVID-19 also depends on this mode of transmission needs further confirmation. However, current data have confirmed that close contact during living together, working, or diagnosis and treatment can result in transmission.^{5,Reference Chan, Yuan and Kok12,Reference Rothe, Schunk and Sothmann17}

Other Transmission Routes

During the course of the SARS epidemic, the possibility of transmission by means of the digestive tract cannot be ruled out because of lack of direct evidence. However, a study reported that there were digestive tract symptoms after COVID-19; whether the transmission was achieved through the digestive tract was unknown and needs further epidemiological study.^{Reference Chen, Chen and Deng21} To date, it is confirmed that SARS-CoV-2 viral RNA can be detected in feces after recovery, which is very similar to the SARS-CoV infection.^{Reference Holshue, DeBolt and Lindquist22} It is unknown whether the virus is infectious at that time. However, enhanced control measures of the digestive tract products may reduce the risk of its spread during the epidemic.

To date, there is no evidence of transmission by blood, sexual contact, vertically from mother to fetus, or other routes. There is no evidence that flies, mosquitoes, cockroaches, and other arthropods can transmit COVID-19.

Natural Factors

According to data of respiratory diseases, poor ventilation, environmental conditions, and mass gathering indoors will favor the transmission of infectious diseases. Some person-to-person transmissions may be explained by closed environments.^{Reference Phan, Nguyen and Luong11,Reference Chan, Yuan and Kok12} As is well known, the SARS outbreak ceased with the coming of the summer, and it seems there is a direct relationship between the seasonal factors and the spread of this coronaviruses infection among human beings. Therefore, further investigated is needed as to whether the epidemic of COVID-19 relates to meteorological conditions, seasonality, geographical conditions, and ecological environment. The pandemic of COVID-19 occurred in the northern hemisphere and the southern hemisphere, and this fact means that infections of SARS-CoV-2 may not be influenced by temperature.

Social Factors

High population density, high mobility, poor health conditions, and poor health habits are important aspects prompting the spread of infectious diseases. Large cities with concentrated populations and convenient transportation are prone to outbreaks and the prevalence of respiratory infectious diseases. Ineffective prevention and control measures and improper personal hygiene habits and protective measures of medical staff may cause the occurrence of nosocomial infections. The rapid spread of SARS is closely related to mass migrations using modern transportation. The prevalence of COVID-19 increased rapidly in a short period, also demonstrating that current transportation modes are crucial for the spread of this disease. Therefore, it is very important to cut off all responsible transmission routes (through various means) once the transmission routes of the disease are well defined.

According to established prevention and control of infectious disease strategies, areas may be declared epidemic areas after an outbreak of an infectious disease, and corresponding control measures enacted. After the outbreak of COVID-19, Wuhan city has been closed (locked down) since January 23, 2020, and the control measures have been in effect from February 5, 2020. Also, according to a study, “close the city” has reduced the incidence of infection and death by nearly 70%.^{Reference Shen, Peng and Xiao23} In addition, the state vigorously publicized the epidemic control measures, which also played an important role in the control of COVID-19 in China.

With the ending of the Spring Festival holiday, people began to return home to their cities (city-returning). There were 4 relatively large zones where people were returning to, namely Beijing, Tianjin, and Hebei; the Yangtze River Delta; the Pearl River Delta; and Chengdu and surrounding areas. It was previously predicted that, with the large number of people moving back to specific areas, the number of new infections would also increase. Therefore, the epidemic could worsen because of the breakdown of the prevention and control measures. Fortunately, at the time of this writing, the epidemic of the COVID-19 is under control in these 4 regions, as well as in China.

The Epidemic of COVID-19 Outside China in the Early Period

From the first case in Wuhan in November 2019 to the first case of COVID-19 in Thailand on January 8, 2020 (the first case outside China), COVID-19 had successively appeared in other countries. With the spread of the epidemic, it was listed as a public health emergency of international concern (PHEIC) by WHO on January 30, 2020.

The epidemic curve of COVID-19 worldwide showed that early cases occurred sporadically, but the number of cases increased significantly after February 10, 2020 (Figure 4). The mode of infection increased gradually from the visit to Wuhan to the contact with the residence. As shown in the data, most of the cases were initially exposed to Hubei (or Wuhan), or were related to taking transportation or going to Hubei (or Wuhan).²⁴ However, some cases in the later period were related to contact with patients.^{Reference Phan, Nguyen and Luong11} At the time of this writing, the pandemic is roaring all around the world.

FIGURE 4 Epidemic Curve of COVID-19 Cases (n = 319) Identified Outside of China, by Date of Reporting and Travel History, February 10, 2020.^{Reference Shen, Peng and Xiao23}

The Epidemic of COVID-19 in China

Official reports showed a rapid increase in cases of COVID-19 was observed in the epidemic curve. With the coming of the city-returning peak (people returning to their home and work city after the Spring Festival holiday), it was warned that more cases would be reported in other places of China. An epidemic curve is presented (Figure 2), in which, an increase trend in the early course and a down trend in the later period. Although some studies thought that numbers of cases were seriously underestimated, fortunately the down trend has maintained, and this means the epidemic is under control in China.^{Reference Wu, Leung and Leung20}

Occupation, Age, and Gender

During the early period of the epidemic, limited data were obtained for describing the epidemiological characteristics of COVID-19. However, according to 2 published studies, the source of infection was located to the Huanan seafood market. For this reason, the personnel related to the seafood market could be roughly divided into 3 categories: the first category was the dealers and the managers of the seafood market (who had close contact with the seafood market); the second category was the buyers at the seafood market (who had contact history with the seafood market); the third category was the secondary cases of the infections in the seafood market (who had no contact history with the seafood market).^{Reference Li, Guan and Wu3,Reference Huang, Wang and Li4,Reference Chen, Zhou and Dong25}

Among the 425 patients reported by Li et al., the first time period was before January 1 (the date of closing the Huanan seafood wholesale market). The average age of 47 patients was 56 years (26–82 years), and 77% of them were under 64 years old.^{Reference Li, Guan and Wu3} According to the common assumption, the first group (the dealers or the managers of the seafood market) should account for a large part of the affected population in this period, and there were no children under the age of 15 at this stage. In the period after the closure of the seafood market, ie, the second and third stages in the study by Li et al., 3 groups of people (close contact, contact, and no contact with the seafood market) may exist. At this time, the average age of patients was 60 years (15–89 years old) (Figure 5). However, SARS-CoV-2, as a new virus, the people with the highest risk were those people with low resistance, such as the elderly, especially the elderly with underlying diseases, where infections may be more severe. That means the weak more easily contracted infection, with more serious outcomes. This phenomenon has been observed in other binfluenza virus infections, such as the H7N9 virus, which affected the elderly at a higher significantly rate than other common pathogens.^{Reference Wei, Zhao and Gao26}

FIGURE 5 Age Distribution of 425 patients With COVID-19 (Revised From Data of Li et al.^{Reference Li, Guan and Wu3}).

Therefore, it could be preliminarily considered that the main personnel before closure of the market were the dealers or the managers of the seafood market, the purchasers at the seafood market, and the secondary cases of the infected persons in the seafood market. After the closure of the market, onsets of the early stage of infections and secondary transmissions were more likely to affect the elderly with underlying diseases. Therefore, in the follow-up prevention and control of the epidemic, more attention should be paid to the elderly, especially the elderly with underlying diseases; high death rates reported verified this hypothesis now.

Data showed that the proportion of men in the first period was higher (66%); in the second period, the proportion of men decreased (59%); and in the third period, the proportion of men was almost the same as women (48%). This phenomenon confirms the stronger relationship with age; in other words, there was no significant gender difference in COVID-19. This point was confirmed by WHO published data with 716,570 cases reported on April 18, 2020.²

Regarding occupational characteristics, the proportion of medical staff in the cases changed gradually in the 3 periods. It is suggested that, in the process of fighting against the epidemic, the medical staff had a great risk of infection, so it is necessary to ensure the medical equipment of the front-line medical staff. Basic preventive measures, such as wearing masks, gloves, washing hands frequently, and wearing isolation clothes, can stop the spread of the disease. With the spread of the pandemic of COVID-19 out of China, more and more medical staffs were infected, especially for the countries not well prepared. Therefore, it is urgent to strengthen preparedness for medical staff by ensuring adequate amounts of proper equipment for every country.