Clinical predictors of Covid-19 mortality in a tertiary hospital in Lagos, Nigeria: A retrospective cohort study.

Background: The predictors of mortality among patients presenting with severe to critical disease in Nigeria are presently unknown. Aim: The aim of this study was to identify the predictors of mortality among patients with COVID-19 presenting for admission in a tertiary referral hospital in Lagos, Nigeria. Patients and Methods: The study was a retrospective study. Patients' sociodemographics, clinical characteristics, comorbidities, complications, treatment outcomes, and hospital duration were documented. Pearson's Chi-square, Fischer's Exact test, or Student's t-test were used to assess the relationship between the variables and mortality. To compare the survival experience across medical comorbidities, Kaplan Meir plots and life tables were used. Univariable and multivariable Cox-proportional hazard analyses were conducted. Results: A total of 734 patients were recruited. Participants' age ranged from five months to 92 years, with a mean ± SD of 47.4 ± 17.2 years, and a male preponderance (58.5% vs. 41.5%). The mortality rate was 9.07 per thousand person-days. About 73.9% (n = 51/69) of the deceased had one or more co-morbidities, compared to 41.6% (252/606) of those discharged. Patients who were older than 50 years, with diabetes mellitus, hypertension, chronic renal illness, and cancer had a statistically significant relationship with mortality. Conclusion: These findings call for a more comprehensive approach to the control of non-communicable diseases, the allocation of sufficient resources for ICU care during outbreaks, an improvement in the quality of health care available to Nigerians, and further research into the relationship between obesity and COVID-19 in Nigerians.

Sequence effects on the relative thermodynamic stabilities of B-Z junction-forming DNA oligomeric duplexes.

Circular dichroism (CD) and ultraviolet absorption techniques were employed in characterizing the sequence-dependent thermodynamic stabilities of B-Z junction-forming DNA duplexes. The Watson strand of the duplexes has the general sequence (5meC-G)4-NXYG-ACTG (where N = A or G and XY represents all permutations of pyrimidine bases). Duplexes were generated by mixing stoichiometric amounts of the complementary strands. Circular dichroism studies indicate that each duplex is fully right-handed at low salt (e.g., 115 mM Na+) but undergoes a salt-induced conformational transition to a structure that possesses both left- and right-handed conformations at high salt (4.5 M Na+), and hence a B-Z junction. Optical melting studies of the DNA duplexes at fixed DNA concentration with total Na+ concentration ranging from 15 mM to 5.0 M were determined. A nonlinear dependence of the melting temperature (Tm) on [Na+] was observed. Thermodynamic parameters at Na+ concentrations of 115 mM and 4.5 M with a wide range of DNA concentrations were determined from UV optical melting studies via construction of van't Hoff plots. A change of a single dinucleotide within these duplexes significantly affected the helix stabilities. The experimentally obtained free energies for the duplex to single-strand transitions were in close agreement with predicted values obtained from two different methods.

Effect of base pair A/C and G/T mismatches on the thermal stabilities of DNA oligomers that form B-Z junctions.

The thermal stabilities and structures of B-Z junction forming DNA duplexes possessing A/C or G/T base pair mismatches were compared to those of corresponding duplexes possessing perfect matched base pairs. The upper strands of the duplexes have a generalized sequence 5'-(5meCG)-LMN-GACTG-3', where L stands for A or G while M and N are permutations of pyrimidines. The lower strands were either complementary or were such as to create an A/C or G/T mismatch at the position corresponding to L, M, or N. Optical melting and circular dichroism studies were used to investigate the thermal stabilities and structures of both the mismatched base pair and the perfect matched base pair duplexes. Incorporating mismatched A/C or G/T base pairs did not noticeably affect the conformations of the duplexes in 115 mM Na+ but resulted in perturbed B-Z conformations at 4.5 M Na+. For any mismatched base pair duplex, the B-DNA domain of the hybrid B-Z structure formed at 4.5 M Na+ is significantly perturbed while the Z-DNA domain is less perturbed by the presence of the mismatched base pairs. The presence of a mismatch destabilizes a duplex relative to the perfect matched base pair duplex by 1.7-10.0 kcal/mol depending upon position of the mismatch, type of mismatch base pair involved, and Na+ concentration. The thermodynamic destabilization of a mismatched base pair duplex relative to the perfect matched base pair duplex arises from perturbations in nearest neighbor interactions and hydrogen bonding. In general, we observed that the incorporation of an A/C or G/T base pair mismatch in place of a perfect matched base pair at or near a B-Z junction results in a relatively large change in enthalpy and entropy to produce a significant change in the free energy of the duplex to single strand transition. At 4.5 M Na+, where the duplexes possess perturbed B-Z junctions, the farther away from the junction that the mismatch is, the greater the extent of the destabilization.