Time Length of Negativization and Cycle Threshold Values in 182 Healthcare Workers with Covid-19 in Milan, Italy: An Observational Cohort Study

Abstract

Background: Coronavirus Disease 2019 (COVID-19) has rapidly spread worldwide, becoming an unprecedented public health emergency. Rapid detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) suspected cases is crucial to control the spread of infection. We aimed to evaluate the time length of negativization from the onset of symptoms in healthcare workers (HCWs) with COVID-19, and to evaluate significant variations in cycle threshold (CT) values and gene positivity (E, RdRP, and N genes) among positive individuals who returned to work. Methods: We retrospectively analyzed a consecutive cohort of 182 SARS-CoV-2-positive HCWs in Milan, from 16 March to 30 April 2020. Nasopharyngeal swabs were tested by RT-PCR. Results: Asymptomatic HCWs were 17.6% (32/182), and 58 healed at 30 April 2020. The median time length of negativization was 4 weeks (35% of symptomatic versus 40% of asymptomatic HCWs). Four HCWs, healed at 30 April, turned positive within three weeks during controls set up in the work unit. Three-gene positivity had the greatest variability, and increasing CT values from single- to three-gene positivity among all age groups were observed. Conclusions: Self-isolation longer than two weeks and prolonged follow-up periods for the staff returning to work after COVID-19 could be the most suitable choices to counter the SARS-CoV-2 spread. Further studies are needed to investigate infectiousness profiles among positive individuals.

Keywords: Coronavirus Disease 2019; Cycle Threshold values; Reverse Transcription PCR; SARS-CoV-2; health care workers.

Figure 1

Flowchart for the management of healthcare workers (HCWs) with suspected or confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. According to the procedures implemented by Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, all HCWs suspected of SARS-CoV-2 infection must be tested by RT-PCR analysis of nasopharyngeal swabs and, if necessary, put into isolation for at least 14 days. The following criteria had to be met for discontinuation of quarantine: (a) resolution of respiratory symptoms and an apyretic state lasting longer than 72 h, and (b) two consecutively negative RT-PCR test results obtained on swabs collected at least 24 h apart. The same procedures were used for asymptomatic HCWs, with the exception of criteria (a).

Figure 2

Timeline of cycle threshold (CT) value collection. An example according to a time length of negativization of 4 weeks.

Figure 3

Distribution of gene positivity and mean cycle threshold (CT) values among different age groups. (A) Box-plot of mean viral load (cycle threshold) across different ages according to gene positivity. Empty circles represent a single observation for each gene. (B) Box-plot of mean viral load at baseline for the gene positivity E–RdRP–N among different age-groups. Empty circles represent a single observation for each age group.

Figure 4

Time at which HCWs, stratified by gene positivity, became negative.