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.