Introduction
Since 2019, the world has seen a rapid and wavelike spread of the
coronavirus disease 2019 (COVID-19). Between 2019 and December 2022,
more than 650 million confirmed cases and over 6.6 million deaths were
reported globally. The original strain of COVID-19 was Alpha B.1.1.7.
Beta B.1.351 variant was first reported in South Africa in May 2020,
whereas the Gamma P.1 variant was isolated by Brazilian scholars for the
first time in November 2020. The Delta B.1.617.2 variant was first
isolated in October 2020 in India [1,2]. Lambda variant first
appeared in Peru in December 2020 and has since spread to at least 41
countries and regions worldwide [3]. The Omicron variant originally
reported in Southern Africa spread globally at a significantly higher
rate than the Delta variant in November 2021. It has proven to be
the dominant influenza strain in most parts of the world. Initially, the
dominant Delta variant appeared to cause more severe disease while
spreading at a lower speed than the current B.1.1.529. However, Omicron
variant is more transmissible, spreads faster, and has a shorter
incubation period [4]. The aerosol of the variant can survive after
a long period, among the Omicron identified, BA. One variant can survive
for 193.5 h on the surface of plastic products, which is 3.5 and 1.7
times longer than the original and Delta strains, respectively
[5-6]. Immune escape and breakthrough infections can occur easily in
vaccinated populations after infection with Omicron subvariants [7].
New neutralizing antibodies are used in antiviral therapies [8].
Currently, the most widely used long-acting neutralizing antibodies are
tixagevimab and cilgavimab [9,10]. Besides the immediate protection
against COVID-19 from monoclonal antibodies (mAbs), an increasing number
of antiviral drugs have been effective in the treatment of patients with
COVID-19 [11-15]. The US FDA emergency use authorized paxlovid, a
co-packaging box consisting of nirmatrelivr and the viral protease
enhancer ritonavir (Pfizer Pharmaceutical Co., Ltd.) for the treatment
of COVID-19 on November 22, 2021. Paxlovid acts on the main protease of
SARS-CoV-2, inhibiting the processing of protein precursors mediated by
this enzyme and viral replication, and significantly reduces mortality.
Nirmatrelivr has a significant antiviral activity, and reduces the viral
load most rapidly and has similar antiviral activity for α, γ, δ, λ, and
Omicron variants [16]. Azvudine
(2’-deoxy-2’-β-fluoro-4’-azidocytidine) (FNC) is the first SARS CoV-2
small-molecule drug developed and successfully marketed in China. The
target of Azvudine is RdRp, which is a pathway that increases the
indications for anti-HIV drug-based COVID-19 treatment. In a phase III
clinical trial, 40% patients with COVID-19 showed alleviated clinical
symptoms 1 week after receiving azvudine treatment, while the proportion
of patients receiving placebo was only 11% [23].
Respiratory failure and hypoxemia are the main manifestations of
COVID-19, and kidney involvement is also common [17, 18]. Solid
organ transplant recipients (SPTR) are at high risk of infections,
including COVID-19, by various pathogens owing to long-term
immunosuppressive medication.
Regarding the treatment of kidney transplant recipients (KTR) infected
with COVID-19, one of the challenges is protecting the function of the
transplanted kidney while adjusting the immunosuppressant. No consensus
exists on the adjustment of immunosuppressive drug doses in confirmed
COVID-19 KTRs. Although immunosuppression may prevent an effective T
cell response against COVID-19, it also helps to control the
inflammatory reaction, which is an important cause of COVID-19 disease
progression and death [19]. Another challenge in the treatment of
COVID-19 after transplantation is that it is neither normal nor
standard. Therefore, investigating kidney transplant patients with
COVID-19 and administering small-molecule drugs therapy can pave the way
for better prognosis of KTR. Since the COVID-19 outbreak, we have taken
the lead in conducting clinical trials on small-molecule drugs for
COVID-19 in China.