Viral kinetics of SARS-CoV-2 over the preclinical, clinical, and postclinical period

Abstract

Background: It is necessary to know the viral kinetics and conduct epidemiological investigations of confirmers to prevent the spread of the new infectious disease COVID-19 to the community. To date, no study has been published on viral kinetics during the preclinical and clinical periods of SARS-CoV-2.

Methods: A confirmed case was defined as a patient with positive results by real-time reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV-2. Both specimen types were collected over the whole clinical course in all patients. Asymptomatic patients who had been screened for COVID-19 due to a strong epidemiological link were also enrolled. The study population included 54 hospitalized patients with confirmed COVID-19.

Results: COVID-19 shows a very high viral load on the day of symptom development, which then decreases overall. Rapid viral proliferation was observed 0-5 days before symptoms developed. Cycle threshold (Ct) value was the lowest in the clinical course from 5 days before symptoms to 10 days after symptoms occurred (Ct < 30). The rRT-PCR results were negative approximately 3 weeks after the onset of symptoms. However, there was a continuous pattern that was negative and positive for up to 6 weeks and more.

Conclusion: Considering the characteristic that COVID-19 has a high viral load before symptoms appear, it is necessary to consider to expand the scope of epidemiological investigations. As there is a very low possibility of transmission after 10 days of symptom occurrence, it may be considered to release isolation after 10 days of symptom occurrence in limited resource situations. This study allows for the planning of epidemiological investigations, patient's ward supply, and follow-up of patients through sequential changes in viral loads over the entire clinical course. In addition, it is possible to estimate the clinical time at which the patient is present.

Keywords: COVID-19; SARS-CoV-2; Viral load.

Graphical abstract

Figure 1

Changes in the SARS-CoV-2 Ct value of rRT-PCR in respiratory specimens. (A) Changes in the Ct value of SARS-CoV-2 RNA (RNA-dependent RNA polymerase gene, RdRP) in lower respiratory specimens in 54 patients with COVID-19. (B) Changes in the Ct value of SARS-CoV-2 RNA (RdRP) in nasopharyngeal specimens.

Figure 2

Changes in the SARS-CoV-2 Ct value of rRT-PCR in respiratory specimens. The calculated value as the mean of the Ct value of SARS-CoV-2 RNA(RdRP) in the nasopharyngeal specimens. The Ct value shows the lowest value on the day of symptoms and negative 3 weeks from the date of symptoms. (Negative > Ct value 35).

Figure 3

Changes in the SARS-CoV-2 Ct value of rRT-PCR in respiratory specimens of patient 36. A 71-year-old man with a history of diabetes was hospitalized on the 5th day of cough and fever. On the 10th day of symptom onset, dyspnea worsened and tachypnea persisted even after high flow nasal cannula oxygen therapy. On the 10th day of symptom development, methylprednisolone was administered at 0.5 mg/kg for 3 days and then stopped. Oxygen demand was reduced, but it was worsened on the 4th day after discontinuation, so methylprednisolone was taken at 1 mg/kg for 3 days. (The concomitant drugs used during the period of use of methylprednisolone were nafamostat, piperacillin/tazobactam, levofloxacin, and lansoprazole.) After clinical improvement, the prednisolone dose was reduced and finally stopped after 10 days. In the rRT-PCR test after the discontinuation of corticosteroid administration, the Ct value was continuously decreased and negative was confirmed on the 19th day after the final discontinuation.