Discussion
In May 2023, the global health emergency of COVID-19 was officially terminated by the World Health Organization. The attention for COVID-19 care and treatment has now been redirected towards the vulnerable population who are at a higher risk of developing more serious COVID-19-associated illnesses. In the midst of a widespread Omicron outbreak and high vaccination rates, our study revealed that the utilization of nirmatrelvir-ritonavir did not result in a more rapid elimination of respiratory SARS-CoV-2 in patients at high risk.
Interestingly, the examination centered on individuals who received nirmatrelvir-ritonavir treatment within 10 days after symptoms onset or first positive RT-PCR test. It revealed a faster conversion from positive to negative RT-PCR tests when compared to untreated patients. The study also found that the shorter the time between the onset of symptoms or the first positive RT-PCR test and the administration of nirmatrelvir-ritonavir, the faster the conversion to RT-PCR negativity. This indicates that the timing of nirmatrelvir-ritonavir therapy initiation following the onset of symptoms is a crucial indicator in achieving rapid elimination of the virus. Our findings align with a recent study[19] which indicated that the administration of nirmatrelvir-ritonavir may accelerating the conversion of negative RT-PCR respiratory SARS-CoV-2. Additionally, our study expands upon the findings of the EPIC-HR study[10], which included unvaccinated and non-hospitalized adults from various racial backgrounds. In contrast, our study specifically examined Asian adult patients at high risk who were hospitalized, fully or partially vaccinated and generally “older”.
RT-PCR testing has been utilized to detect SARS-CoV-2 in the upper respiratory tract[20]. The Ct values of RT-PCR represent the number of amplification cycles needed for the target gene to exceed a threshold level, potentially offering semi-quantitative or indirect measurements of viral load[21]. Previous studies have analyzed the temporal trends in Ct values over the course of a SARS-CoV-2 infection. The lowest Ct values (indicating a higher concentration of viral RNA) are observed shortly after the onset of symptoms and are significantly correlated with the time elapsed since onset. Higher Ct values may be linked to better outcomes in COVID-19 individuals, decreased possibility of progression to severe illness, decreased disease severity, decreased mortality, and absence of biochemical and haematological markers[21]. The RT-PCR Ct value was frequently used as an alternative measure of viral load, serving as a measure of infectivieness. According to this research, the administration of nirmatrelvir-ritonavir within 10 days of the symptom onset resulted in a quicker rise in RT-PCR Ct value, thus reducing the duration of isolation. It is reported that early administration of nirmatrelvir-ritonavir in patients could lead to a quicker cessation of virus shedding, thereby reducing the risk of disease transmission and expediting recovery from COVID-19[21].
Previous study noted that SARS-CoV-2 viral replication at multiple sites outside the respiratory tract during the first two weeks after the onset of symptoms[22]. The peak viral load of SARS-CoV-2 typically occured around the time of symptoms onset, followed by a gradual decline[23]. In severely ill patients, viral replication can continue for several months[22]. Based on the findings mentioned above, it should be considered that patients with COVID-19 more than 5 days post-onset and/or severe illness are highly probable to derive benefits from nirmatrelvir-ritonavir therapy. This is due to the continued presence of the virus in the body, particularly in the respiratory system, among patients in the early (within 14 days after symptoms onset), intermediate (15-30 days), and late (31 days or longer) COVID-19 patients. At this time, nirmatrelvir-ritonavir is given to clear the virus, which theoretically benefits the patient’s recovery and may even prevent their death. Furthermore, owing to the scarcity of COVID-19 healthcare facilities in Shanghai during the initial six months of 2022, a number of individuals testing positive for PCR were unable to receive immediate admission following infection, resulting in a disease duration exceeding 5 days upon admission. Therefore, many patients admitted in Shanghai Geriatric Medical Center did not receive nirmatrelvir-ritonavir until RT-PCR was positive or symptoms occurred more than 5 days. The current research validated that administering nirmatrelvir-ritonavir within 5 to 10 days of symptom onset or a positive RT-PCR test could expedite the conversion to a negative result.
The limitation of the current study cannot be ignored. The study is a single-centered retrospective observational study with potential residual confounding and selection bias. Because the study was conducted retrospectively, a detailed analysis of adverse events and rebound were not performed, as the data in medical records regarding these topics were sometime inconsistent.