RESUMEN
Background and aim: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities. Design Setting and participants: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients. Results: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality. Conclusion: These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.
RESUMEN
All retroviruses encode a Gag polyprotein containing an N-terminal matrix domain (MA) that anchors Gag to the plasma membrane and recruits envelope glycoproteins to virus assembly sites. Membrane binding by the Gag protein of HIV-1 and most other lentiviruses is dependent on N-terminal myristoylation of MA by host N-myristoyltransferase enzymes (NMTs), which recognize a six-residue "myristoylation signal" with consensus sequence: M1GXXX[ST]. For unknown reasons, the feline immunodeficiency virus (FIV), which infects both domestic and wild cats, encodes a non-consensus myristoylation sequence not utilized by its host or by other mammals (most commonly: M1GNGQG). To explore the evolutionary basis for this sequence, we compared the structure, dynamics, and myristoylation properties of native FIV MA with a mutant protein containing a consensus feline myristoylation motif (MANOS) and examined the impact of MA mutations on virus assembly and ability to support spreading infection. Unexpectedly, myristoylation efficiency of MANOS in Escherichia coli by co-expressed mammalian NMT was reduced by ~70% compared to the wild-type protein. NMR studies revealed that residues of the N-terminal myristoylation signal are fully exposed and mobile in the native protein but partially sequestered in the MANOS chimera, suggesting that the unusual FIV sequence is conserved to promote exposure and efficient myristoylation of the MA N terminus. In contrast, virus assembly studies indicate that the MANOS mutation does not affect virus assembly, but does prevent virus spread, in feline kidney cells. Our findings indicate that residues of the FIV myristoylation sequence play roles in replication beyond NMT recognition and Gag-membrane binding.
