Assessing the Prevalence of Anemia Post-COVID-19 Infection in Adult Members of a Southeastern U.S. Integrated Healthcare System (preprint)

Background COVID-19 may cause or worsen anemia, leading to fatigue, lower quality of life, increased risk of comorbidities, and significantly associated with worse outcomes in patients hospitalized with COVID-19. Little is known among a community-based population. We aimed to investigate the incidence and risk factors of anemia post-COVID diagnosis in a community-based population. Methods We identified all adult members of KPGA with a confirmed diagnosis of COVID-19 between January 2020 and March 2022 and followed through March 2023. Anemia was defined using hemoglobin (Hgb) labs 180-days (±30-days) and 365-days (±30-days) after COVID-19 diagnosis and sex-specific thresholds. Potential risk factors included demographics and clinical characteristics (defined by diagnosis codes) at the time of COVID-19 diagnosis. Hospitalization with COVID-19 was used as a marker of COVID-19 severity. Logistic regression among individuals not diagnosed with anemia pre-COVID investigated the association between each risk factor and anemia 180- and 365-days post-COVID-19 infection. We stratified fully adjusted model by hospitalization with COVID-19 to assess effect modification. Results We included 3,450 and 3,043 individuals who met the inclusion criteria and had Hgb results available 180- and 365- days post-COVID-19 diagnosis. One-third of our population had anemia 180-days (n=1,100, 32.17%) and 365-days (n=1,007, 33.09%) post-COVID-19, with approximately 11% of the cohort being newly diagnosed cases of anemia. In the fully adjusted models females (vs. males) (OR=1.71, 95% CI: 1.42, 2.06), Black or African American individuals (vs. non-Black individuals) (OR=2.34, 95% CI: 1.98, 2.76), adults diagnosed with kidney disease (OR=1.79, 95% CI: 1.42, 2.25) or diabetes  (OR=1.26, 95% CI: 1.12, 1.64), and adults hospitalized with COVID-19 (OR=1.43, 95% CI: 1.15, 1.78) were more likely to be diagnosed with anemia 365-days after COVID-19 diagnosis. Analyses stratified by hospitalization status showed a possible effect modification between hospitalization status and post-COVID-19 anemia. Discussion Our study showed that one in three people in a community-based population have anemia 180-days and 365-days after their first COVID-19 diagnosis. Anemia can cause fatigue, a lingering symptom of COVID-19 infection. Though more research is needed, ongoing surveillance of COVID-19 patients for anemia may be an important component of management of long COVID-19.

Evaluation of SARS-CoV-2 Main Protease Inhibitors Using a Novel Cell-Based Assay

As an essential enzyme of SARS-CoV-2, main protease (MPro) triggers acute toxicity to its human cell host, an effect that can be alleviated by an MPro inhibitor. Using this toxicity alleviation, we developed an effective method that allows a bulk analysis of the cellular potency of MPro inhibitors. This novel assay is advantageous over an antiviral assay in providing precise cellular MPro inhibition information to assess an MPro inhibitor. We used this assay to analyze 30 known MPro inhibitors. Contrary to their strong antiviral effects and up to 10 μM, 11a, calpain inhibitor II, calpain XII, ebselen, bepridil, chloroquine, and hydroxychloroquine showed relatively weak to undetectable cellular MPro inhibition potency implicating their roles in interfering with key steps other than just the MPro catalysis in the SARS-CoV-2 life cycle. Our results also revealed that MPI5, MPI6, MPI7, and MPI8 have high cellular and antiviral potency. As the one with the highest cellular and antiviral potency among all tested compounds, MPI8 has a remarkable cellular MPro inhibition IC50 value of 31 nM that matches closely to its strong antiviral effect with an EC50 value of 30 nM. Therefore, we cautiously suggest exploring MPI8 further for COVID-19 preclinical tests. A cell sorting-based assay was developed to study about 30 SARS-CoV-2 main protease inhibitors, revealing MPI8 as the most potent one and others with likely different mechanisms.