Background: The rapid increase in COVID-19 cases puts significant stress on the health system. Healthcare workers (HCWs) who are at the frontline responding to the crisis are particularly susceptible to this highly transmissible infection, given their long and close exposure to infected persons. Decision-makers are in need of the information to appropriately determine a quarantine guideline and policy for healthcare workers while maximizing the patient’s safety and ensuring the continuous provision of services to society. Objectives: The primary objective of this study is to develop recommendations for quarantining HCWs who have been exposed to COVID-19. The secondary objectives are 1. to estimate the proportion of HCWs with COVID-19 by nucleic-acid amplification test (NAAT) within the quarantine period and the difference in proportions of HCWs with COVID-19 by NAAT at day 5, 10 and 14 of the quarantine period; 2. to descriptively report the incubation period (from the date of exposure to COVID-19 source case to when the symptom first appear (symptomatic case) or to when the NAAT is positive (asymptomatic case); and 3. to estimate the proportion of asymptomatic COVID-19 among those HCWs with COVID-19. Methods: This is a prospective cohort study to identify the incidence of COVID-19 among health care workers who had been in contact with COVID-19 cases. The inclusion criteria were HCWs aged over 18 years old who have been identified as HCWs in which a patient with laboratory confirmed COVID-19 infection is receiving care or ‘HCWs contact’. Following the initial routine test (Nucleic acid amplification tests, RT-PCR), if the result is PCR negative ‘HCWs contact’ with or without any respiratory symptoms and works in a health care facility were included for this study. The sample size calculation was 375 participants. Data collection included 1) daily self-monitoring symptoms and temperature for 14 days, 2) Nasopharyngeal & oropharyngeal swabs and saliva at day 5, 10 and 14 of the quarantine period and 3) serum at day 0 and 14 of the quarantine period. For confirmation of COVID-19 cases, it was based on detection of unique sequences of virus RNA by Nucleic acid amplification tests such as real-time reverse-transcription polymerase chain reaction (rRT-PCR) from nasopharyngeal & oropharyngeal swab and saliva samples at day 5, 10 and 14. For monitoring purposes, serum immunoglobulin G (IgG) were analyzed by ELISA for antibody against SAR-CoV-2 virus at day 0 and 14 of the quarantine period. Results: From January to July 2021, 153 eligible health care workers met the inclusion criteria and provided consent. Most participants were women (84%), age range between 22 and 63 (mean age, 34 years old) and worked as nurses (52%), assistant nurses (14%), doctor/dentist/pharmacist/laboratory staff (20%) or other supporting HCWs (15%). Most of the participants worked at an emergency room (ER) or intensive care unit (ICU) (41%). Most of the participants reported to have been vaccinated (78%) and only 5% of the HCWs reported to have full PPE when exposed to COVID-19 patients. Three HCWs were tested positive for SARS-CoV-2, giving the positivity rate of 2.08% (95%CI: -0.28% to 4.44%) of the HCW contact which was detected at day 5 for 2 HCWs and at day 10 for 1 HCW. All three HCWs received 2-dose COVID-19 vaccination (Sinovac) at an average of 40 days before the contact. They did not use the complete set of PPE and were only put surgical masks and gloves on while in contact with COVID-19 patients. This study reported the incubation period from the date of exposure to known COVID-19 source to when the PCR positive is positive of 6.33 days. Two out of three (66%) COVID-19 positive cases are symptomatic. The overall positivity rate for SARS-CoV-2 serostatus from the blood sample was 84.15% (95%CI: 76.07% to 92.22%) at day 0-5 and 79.07% (95%CI: 71.96% to 86.18%) at day 14. Most of the positivity rates for SARS-CoV-2 serostatus were correlated with vaccination status. The level of anti-SARS-CoV-2 IgG antibody titer from COVID-19 positive HCWs at day 14 ranged between 20,665 to 40,000 AU/mL. During the 14-day monitoring period, health-related quality of life (measured using the EQ-5D-5L) of HCWs decreased due to depression and anxiety domain. On average, the quality of life of HCWs decreased from the baseline up until day 5 of monitoring and increased as the PCR results became available. The decreased quality of life was significantly associated with increasing age and showing signs of respiratory disease. The increased quality of life was significantly associated with those who used the full set of PPE. Discussion: The study can only be carried out after the reopening policy in Thailand was implemented. From January to July 2021, there was a national campaign to encourage healthcare workers to receive COVID-19 vaccination. Around 78% of the healthcare workers were vaccinated against the COVID-19, and 82.8% of these groups received two doses as scheduled. This study did not recruit enough sample sizes, and only 2% of the HCWs were positive for COVID-19.Therefore, it is unclear whether to reduce the number of days of quarantine or be certain about the factors associated with infection. However, this research highlighted that HCWs in all departments are at risk of being exposed to COVID-19 patients. Closely monitoring high-risk COVID-19 contact cases during the first 5 to 10 days after exposure and periodic testing for infection remains essential for controlling the spread of the disease in healthcare facilities. Nurses and axillary nurses who work in emergency departments and intensive care units are at high risk of COVID-19 exposure. HCWs who work directly with known COVID-19 patients may take full precaution and be equipped with a full set of PPE while those working in other departments may have less awareness or lack of adequate protective equipment. The government should therefore focus on supporting PPE for all HCWs and should develop a working system to minimise the risks of being exposed among coworkers such as shift arrangement. Additional supports for HCWs to tackle mental health issues and compensation in various forms should also be considered. Recommendations: 1. Closely monitoring of healthcare workers who had been in high-risk contact with COVID-19 patients for 5 to 10 days remains necessary even if personnel have been vaccinated. 2. A booster dose of COVID-19 vaccination for healthcare workers is still necessary to control the epidemic. 3. The government should procure and distribute sufficient Personal Protective Equipment (PPE) for all healthcare workers who were on duty whether working directly with COVID-19 patients or not. This is because all personnel are at risk of coming into contact with COVID-19 patients who have no symptoms. 4. The government should have measures to support healthcare workers who perform their duties to ease mental health problems.