It is well understood that confirmed patients with COVID-19 are the main sources of infection in human-to-human transmission of COVID-19. Asymptomatic cases and superspreaders may also be potential sources of infection. Additionally, other patients with low immunity and infected patients with no or only mild symptoms may gather in hospital to spread the virus in the community through social interactions. Thus, nosocomial infection acts as a contributing factor of an outbreak (11,12).

AsymptomatiC patients are those without clinical manifestations but with positive nucleic acid results of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or chest imaging (13). Asymptomatic individuals may not be ill enough to seek medical care, and this allows them to participate in a larger range of activities. Wang et al (14) stated that the transmissibility of asymptomatiC patients was fairly limited due to the lack of symptoms, including coughing and sneezing. Hence, they are unlikely to be the major driving force of transmission (14). However, Li et al (15) demonstrated that 86% of all patients with COVID-19 infection in China were asymptomatic individuals in the early stage, and they caused 79% of the documented COVID-19 cases with observed symptoms and the rapid spread throughout the country before the travel restrictions. These studies indicate that the discussion on COVID-19 transmissibility of asymptomatic individuals remains to be clarified.

Progress in COVID-19 containment has revealed that the proportion of asymptomatic individuals was higher than previous projections in Wuhan, China (40-50% of all cases) (16). However, some studies have shown that this proportion may be as low as 10% (16,17). It has been reported that asymptomatic individuals can be divided into inapparent cases, which do not appear symptomatic for the incubation period and can even obtain positive results from laboratory tests, and presymptomatic cases (17). During the incubation period, presymptomatic individuals can transmit COVID-19 even before onset of clinical symptoms (18). He et al (18) found that the highest infectiousness occurred before symptom onset, and 44% of secondary cases originated from presymptomatic cases. Kimball et al (19) reported that a rapid transmission of COVID-19 occurred in a skilled nursing facility in King County (WA, USA). About half of infected individuals were asymptomatic or presymptomatic on the day of nucleic acid testing, and they may therefore contribute to the transmission of COVID-19 (19).

Individuals who have a greater than average capability of infecting more people are known as superspreaders (20). Medical experts have claimed that superspreaders may trigger a fresh outbreak (19). It is hence necessary to analyze the epidemic chain of transmission of COVID-19 originating from a superspreader considering the increased strain virulence, and the differences in hosts and co-infection with another pathogen should be taken into account (21). Additionally, asymptomatic and mild symptomatic individuals may be another type of infection source of superspreading events (SSEs) due to lack of awareness and containment measures (22). In addition, the combined effects of biology, behavior and environmental factors may lead to superspreading events (20).

During SARS and Middle East Respiratory Syndrome outbreaks, nosocomial transmission was associated with SSEs, and numerous patients, including HCPs and ACPs, were infected with those events (23). Additionally, hospitals are relatively closed environments with often dense populations and poor ventilation, and are therefore more likely to be a transmission site compared with an open environment (24). Moreover, unrecognized or misdiagnosed infection cases in 11 directly transmitted infections, including SARS, were shown to be the main reason of SSEs, followed by the mode of transmission, contact frequency and co-infection (25).

In addition to the aforementioned scenarios, SARS-CoV-2 was detected in some discharged patients, who may still be potential virus carriers (26). Furthermore, it was reported that reverse transcription PCR test results may not fully correlate with transmissibility (27). The World Health Organization (WHO) suggests that patients should be released from isolation >10 days after symptom onset and after >3 additional days without symptoms (28).

COVID-19 primarily spreads via air droplets and direct contact, but SARS-CoV-2 RNA can also be found in fecal specimens and the virus may be spread via an excretory route (29). Although neonatal infections of COVID-19 have been observed, there is no direct evidence of vertical mother-to-child transmission (30). Fan et al (31) analyzed two confirmed expectant mothers, and SARS-CoV-2 was not detected in any of the products of conception and newborns. This analysis indicated that the risk of vertical transmission route of COVID-19 was relatively low (31).

Liu et al (32) reported that the trace of SARS-CoV-2 RNA was extremely high in small and non-ventilated mobile toilets in public areas of two hospitals in Wuhan (China), and relatively low in the isolation and ventilated rooms. Notably, some cases of HCP infection in China were associated with aerosol transmission in relatively closed environments, long-term exposures and high-concentration pathogen aerosol environments (33,34). The size of droplets is variable due to the force and pressure at emission, evaporation and environment influence; droplets (5-10 µm in diameter) remain in the air for a short time and settle within 1 m of the source, while aerosols (≤5 µm) disseminate in the air over long distances (35,36). A large droplet can become an aerosol in less than a second (35). van Doremalen et al (37) reported that SARS-CoV-2 is viable and infectious in aerosols for 3 h. It has been shown that the virus can still be detected at a distance of 4 m from patients (38). If considering only the droplets and direct contact transmission of COVID-19, the recommended distance for HCPs from patients can be decreased to 1 m (35).

Patients of all ages are susceptible to COVID-19, especially elderly males (>55 years old) with underlying diseases, such as diabetes, hypertension and cardio-vascular disease (39). Hospitalized patients in nursing homes or skilled care facilities with moderate to severe asthma, severe heart disease or low immunity (cancer, immunodeficiency or severe obesity) are all high-risk COVID-19 populations of endogenous infection (40).

Another noteworthy aspect of endogenous infection is healthcare-associated infections for critically ill patients caused by other pathogenic microorganisms. For example, ventilator-associated pneumonia (VAP) is the most common complication of mechanical ventilation (41). The estimated mortality of VAP is 13% (41). Zhou et al (42) reported that secondary infections occurred in 27/57 non-survivors of COVID-19, and VAP occurred in 10/32 patients who underwent invasive mechanical ventilation. He et al (43) reported that the nosocomial infection rate among patients with COVID-19 was 7.1%; the most common infection was pneumonia, followed by bacteremia and urinary tract infection. The pathogens involved were Coagulase negative staphylococcus (27.9%), Acinetobacter (20.9%), Pseudomonas aeruginosa (14%), Enterococcus faecium (11.6%) and Klebsiella pneumoniae (9.3%) (43). Under these circumstances, the death rate among patients with nosocomial infection was 15.4% (43).

In the early stages of the COVID-19 outbreak, a large number of hospitals established 3- or 4-tiered patient triage strategies to reduce contact between the susceptible population and potential sources of infection (48,49). At these hospitals, nurses prescreen patients at the entrance of the main lobby by checking the body temperature and scanning health QR codes. The three colors of QR codes (red, yellow and green) correspond to different risk levels (49). Patients would then be divided into different groups according to their body temperatures (Fig. 2).

Patients with a high body temperature would be transferred to a fever clinic through specific routes, accompanied by HCPs with sufficient protection, and epidemiologists would perform detailed COVID-19 checks (48). Other patients with no fever would be allowed for entrance into the general clinic, and specialists of all departments would prescreen for suspected cases according to the patients' body temperatures, epidemiological histories and QR codes (49). Patients with an epidemiological history, including a history of visiting the epidemic area within 14 days, contacting patients with symptoms suggestive of COVID-19 or from an epidemic area within 14 days, and epidemiological linkage with COVID-19, but with normal body temperatures would also receive the same treatments in different areas, while asked to stay in an isolation room for further treatment (48). The suspected patients' condition would be registered in detail and reported to the relevant departments (48).

Reconciling the mismatch between hospital capacity and a large number of patients in a short-term period is a thought-provoking process. Currently, appropriate self-isolation is emphasized for most self-healing and suspected patients to reduce unnecessary visits to the hospital. There are a number of additional tools for reducing the consumption of unnecessary medical resources, such as mobile applications that can track geographic routes so that patients can self-report their own physical conditions and test results of COVID-19. Healthcare institutions can then find out where the outbreak centers are and take corresponding measures and allot materials by analyzing the data collected through these apps (50). Canadian scientists suggested that suspected patients with COVID-19 may be detected and monitored at home while equipped with instruments for measuring body temperature, blood pressure and heart rate (51). Additionally, HCPs can communicate safely with patients through remote monitoring systems (51). The effectiveness of home care depends on factors including professional guidance and management, and adequate measurements for nursing at home in cases of suitable conditions of the patients (52).

Furthermore, patients can be screened by telephone before they enter the hospital in order for HCPs to prepare for isolation before patients who need urgent care arrive to the hospital (53). In addition, internet hospitals in China provide medical consultation services for the public in order to alleviate the public's alarm, impart personal protection knowledge and correct inappropriate medical behaviors, thereby reducing unnecessary visits to hospitals (54).

Frontline HCPs have a distinctly higher risk of infection, especially those who re-use PPE or do not have adequate PPE (55). Htun et al (56) proposed a Staff Health Surveillance System to monitor employee travel experience, sick leave and detailed information, and record body temperature and N95 mask usage. These data provide important references for the management and protection for HCPs.

The Chinese Health Commission specifies that fever clinics are to be divided into special consulting rooms, specifically used for receiving patients with a high risk of COVID-19, and general consulting rooms, to receive patients with a low risk or a clear non-COVID cause of fever (48). These fever clinics, also known as wards, are located in a separate area and the entrance for patients is different from that of healthcare workers (49). The wards provide a convenient way of isolation from the outside and they are divided into two parts: One for isolating confirmed cases, which can host multiple patients, and the other for suspicious patients, where only one person is allowed per room (57). A buffer zone is located between the clean, semi-clean and contaminated areas to reduce staff exposure to infected cases, and HCPs take strict self-protection measures and go through disinfection before entering and leaving the contaminated area (58). Ventilation of the isolation ward is required to reach 60 l/s, and the distances between beds are set to at least 1 m (59). The number of isolation rooms is determined based on the epidemic condition and the number of patients received.

It is important to design and install appropriate isolation procedures, such as physical barriers or partitions to guide patients to different areas, curtains in the shared area to isolate patients, and installing and maintaining air treatment systems with directional, filtering equal capacity to maintain air circulation (60). Tang et al (61) suggested that the doors and windows of the isolation room should be kept closed to avoid reverse airflow.

According to the transmission modes of COVID-19, treatment procedures that produce droplets and aerosols are high risk. Loeb et al (62) demonstrated that auxiliary intubation, suctioning before intubation and operating an oxygen mask were high-risk activities. Patients' secretions, saliva or blood may aerosolize to the environment while receiving treatment, especially in the stomatology department, with possible apparatus contamination (63). Hence, the risk of crossinfection increases through direct contact (63). Moreover, the virus can be detected in conjunctival swabs of patients with eye symptoms (64), indicating that patients who received slit lamp examination and direct ophthalmoscopy, as well as ophthalmologists, have a high risk of infection (65).

Incidentally, each medical department should suspend all unnecessary inspections to decrease the chance of transmission (65); only urgent surgeries should be arranged at the end of the day to reduce the risk of hospital infection (63,66). Additionally, the number of health care assistants should be minimized, and patients who are at different risk levels of infection should be placed separately to reduce cross-infection (67).

The risk of nosocomial infection can be analyzed from two aspects: i) Daily risk of exposure, and ii) Total number of days of exposure. It has been shown that patients in the high daily risk department for a short time may have the same chance to be infected as patients in the low daily risk department for a long time (68). For each department, it is necessary to decrease the daily risk through various protective and disinfection measures, and shorten the treatment time of patients by reducing unnecessary treatment procedures (69).

van Doremalen et al (37) has reported that the half-life of SARS-CoV-2 in aerosol is 1.1-1.2 h and has a longer viability period on stainless steel and plastic surfaces, with half-lives of 5.6 and 6.8 h, respectively. Constant humidity and temperature for an extended period of time in the hospital may further prolong the survival period of the virus (32). Coronavirus is sensitive to ultraviolet light and heat, and most disinfectants (except for chlorhexidine) can effectively inactivate the virus (70,71). Kampf et al (70) reported that using 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite can effectively inactivate human coronavirus within 1 min; however, 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine and gluconate are less effective.

The virus can be widely distributed on the floor, computer mouse, trash cans and even bed handrails, and can be detected in 4 m of air surrounding a patient (38). Compared with contaminated areas, clean and semi-clean areas exhibited more sites where the virus was detected. Moreover, the contamination in isolation wards was even worse than that in ICUs (58,72). These results indicate that HCPs may be exposed to a higher risk in isolation wards and semi-clean areas instead of contaminated areas. Therefore, it is important to enhance daily disinfection, particularly on key surfaces such as handle rails, switches and computer keyboards.

The wards of discharged patients should be fully disinfected. Sheets, curtains, ventilation, lighting and all surfaces should be carefully cleaned (73). For medical procedures that may generate aerosols, effective air isolation measures, including single rooms, negative pressure, frequent ventilation and powered air-purifying respirators, are required (74). Each department should formulate their own disinfection strategies, ensuring that all surfaces are cleaned and disinfected after daily operations (63,65,75).

Transmission through HCP hands in contact with contaminated surfaces also increases the risk of exogenous nosocomial infections (79). Hand cleaning and disinfection are the main steps that can stop pathogens from being transmitted from the patient to the HCP (80). HCPs in all departments need to thoroughly wash their hands before examination, after touching patients, after collecting patients' oral mucosa, blood and body fluids, and after touching equipment without sterilization (81). Pessoa-Silva et al (82) investigated the hand hygiene conditions of 149 newborn nursing staff, and the results revealed that the use of gloves did not completely protect HCP hands from bacterial contamination. Since numerous HCPs still believe that the purpose of using gloves is only for self-protection rather than protecting patients, hand washing compliance needs to be further rein-forced. Hands should also be strictly sterilized before wearing gloves to avoid infection caused by broken gloves (83).

Patients in community or hospital isolation should strictly comply with medical guidance and wash their hands with water or soap for at least 20 sec or with an alcohol-based hand sanitizer, avoid touching their eyes, cover their nose and mouth with tissues when coughing or sneezing, and disinfect objects and surfaces that are always touched (84). Patient education will increase awareness for hand hygiene (85). Based on a survey performed on a Chinese population, 98% of the participants would wear masks when they went outdoors; additionally, participants with a high socioeconomic status, especially females, were more educated about COVID-19 and complied better to PPE usage and hand hygiene guidance (86).

Sufficient knowledge and on-premises work experience may improve the ability of HCPs to better handle COVID-19, since incorrect attitudes and practices directly increase the risk of infection (87). In the early stages of the outbreak, the health administrative department of hospitals in China conducted professional training for medical workers through demonstrations, videos and other methods, including personal protection measures, medical waste disposal and emergency treatment agreements, and experts supervised the entire process of professional training. Before participating in the treatment of COVID-19, HCPs were subjected to medical examination and daily self-monitoring of respiratory symptoms (88). High-risk HCPs who were pregnant, >55 years of age or had a history of chronic diseases or acute fever were exempted from SARS-CoV-2-associated work (89).

During the COVID-19 outbreak, the demand of PPE and medical supplies increased dramatically. Wang et al (90) estimated that the daily demand for masks reached 900 million in China. There were too many medical wastes to be disposed of properly to reduce the potential risk of transmission among HCPs, patients and the public. Different types of waste should be collected in specific containers with labels to avoid accidental injury of cleaning staff and decrease the financial costs on waste disposal (91). Installing temporary disposal facilities and incinerators may relieve the pressure of a sharp increase in waste, and the risk of transportation may be influenced by the haul distance and location of facilities, which should be taken seriously according to economic costs and distance (92). Medical waste disposal procedures include collection and separation of medical wastes, transportation facility, proper waste disposal and staff protection and training (93). The WHO has given detailed advice on waste collection and destruction, as well as personnel training and protection (94). According to this advice, Chinese scientists gave guidance on the disinfection of wastes during the COVID-19 outbreak (95).

With the surge in the number of infected cases, the demand of transportation vehicles and HCPs for transportation of patients and equipment for critically ill patients also increased sharply. Deployment and supply of personnel, equipment and drugs are of significance in treatment efficiency and containment of any epidemic. A fast and economical logistics model should be established according to the outbreak situation in various places. He and Liu (96) proposed that the sensitive-exposure-infection-recovery model may be considered as a basis of predicting the medical needs of various regions and formulating a material distribution plan. The 'Eagle-Eyed Observer' is a logistics support system that can monitor the physiological index of HCPs before and after entering the isolation ward, guide the HCPs to use PPE correctly and deal with used PPE, monitor the patient's situation and ward environment, and even organize medical supplies properly (97).