ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virus.

Due to the COVID-19 pandemic, a series of sequelae, such as fatigue, tachypnea, and ageusia, appeared in long COVID patients, but the pathological basis was still uncertain. The targeted radiopharmaceuticals were of potential to systemically and dynamically trace the pathological changes. For the key ACE2 protein in the virus-host interaction, 68 Ga-cyc-DX600 was developed on the basis of DX600 as a PET tracer of ACE2 fluctuation and maintained the ability in differentiating ACE and ACE2. In the temporary infection model inhaled with the radio-traceable pseudovirus in the upper respiratory tract of male humanized ACE2 (hACE2) mice, organ-specific ACE2 dysfunction in acute period and the following ACE2 recovery in a relatively long period was visualized and quantified by ACE2 PET, revealing a complex pattern of virus concentration-dependent degree and time period-dependent tendency of ACE2 recovery, mainly a sudden decrease of apparent ACE2 in the heart, liver, kidneys, lungs, and so on, but the liver was of a quick functional compensation on ACE2 expression after a temporary decrease. ACE2 expression of most organs has recovered to a normal level at 15 days post inhalation, with brain and genitals still of a decreased SUVACE2 ;  meanwhile, kidneys were of an increased SUVACE2 . These findings on ACE2 PET were further verified by western blot. When compared with high-resolution computed tomography on structural changes and FDG PET on glycometabolism, ACE2 PET was superior in an earlier diagnostic window during infection and more comprehensive understanding of functional dysfunction post-infection. In the respective ACE2 PET/CT and ACE2 PET/MR scans of a volunteer, the repeatability of SUVACE2 and the ACE2 specificity were further confirmed. In conclusion, 68 Ga-cyc-DX600 was developed as an ACE2-specific tracer, and the corresponding ACE2 PET revealed the dynamic patterns of functional ACE2 recovery and provided a reference and approach to explore the ACE2-related pathological basis of sequelae in long COVID.

HIV infection and risk of COVID-19 mortality: a meta-analysis

Background: This meta-analysis aimed to estimate the association of human immunodeficiency virus (HIV) infection and risk of coronavirus disease 2019 (COVID-19) mortality.

HIV infection and risk of COVID-19 mortality: A meta-analysis.

BACKGROUND: This meta-analysis aimed to estimate the association of human immunodeficiency virus (HIV) infection and risk of coronavirus disease 2019 (COVID-19) mortality. METHODS: We systematically retrieved articles published on HIV infection and risk of COVID-19 mortality through PubMed, EMBase, China National Knowledge Infrastructure, WanFang, and Chongqing VIP databases using a predefined search strategy from December 1, 2019 to January 31, 2021. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Cochran Q test and I2 statistics were quantified to measure heterogeneity. Odds ratio (OR) and 95% confidence intervals (CI) were computed and displayed in the form of forest plots. Subgroup analysis was performed to explore the source of heterogeneity. Funnel plot, Begg test, and Egger test were used to assess potential publication bias. Stata software version 11.0 was used to analyze all the statistical data. RESULTS: We included 10 studies with 18,122,370 COVID-19 patients, of whom 41,113 were with HIV infection and 18,081,257 were without HIV infection. The pooled overall results suggested that people living with HIV infection had a higher risk of mortality from COVID-19 than those without HIV infection (OR = 1.252, 95% CI 1.027-1.524). Subgroup analysis showed that people living with HIV infection had a higher risk of COVID-19 mortality than those without HIV infection in the United States (OR = 1.520, 95% CI 1.252-1.845) and in South Africa (OR = 1.122, 95% CI 1.032-1.220); however, no significant association was found in the United Kingdom (OR = 0.878, 95% CI 0.657-1.174). CONCLUSION: Patients with HIV infection should be the emphasis population to prevent the risk of mortality during the clinical treatment of COVID-19 patients.

Potent neutralizing RBD-specific antibody cocktail against SARS-CoV-2 and its mutant.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBDV367F mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.