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.