Background Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23–1.71), dyspnea (RR 2.55, 95%CI 1.88–2.46), diabetes (RR 1.59, 95%CI 1.41–1.78), hypertension (RR 1.90, 95%CI 1.69–2.15). Congestive heart failure (OR 4.76, 95%CI 1.34–16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57–27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19–7.39) and reticular pattern (OR 5.54, 95%CI 1.24–24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

Background Although the incidence of tuberculosis (TB) is higher in males compared to females, the relationship of sex with TB treatment outcomes has not been adequately studied. Methods We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess sex differences in clinical and microbiological outcomes in tuberculosis. Results In our cohort of 2,894 patients with drug-susceptible pulmonary TB (1,975 males and 919 females), males had higher adjusted hazards of 9-month mortality due to all causes (HR 1·43,95%CI 1.03-1.98) and infections (HR 1.70, 95%CI 1.09-2.64) and higher adjusted odds ratio for 2-month sputum culture positivity (OR 1.56,95%CI 1.05-2.33) compared to females. Smear positivity at 2 months was not significantly different (OR 1.27, 0.71-2.27) between the sexes. Among 7,896 articles retrieved, 398 articles were included in our systematic review describing a total of 3,957,216 patients. The odds of all-cause mortality were higher in males compared to females in the pooled unadjusted (OR 1.26, 95%CI 1.19-1.34) and adjusted (OR 1.31, 95%CI 1.18-1.45) analyses. Males had higher pooled odds of sputum culture (OR 1.44,95% CI 1.14-1.81) and sputum smear (OR 1.58,95%CI 1.41-1.77) positivity, both at the end of the intensive phase and upon treatment completion. Conclusions Our retrospective cohort showed that male TB patients have higher 9-month all-cause and infection-related mortality, with higher 2-month sputum culture positivity after adjusting for confounding factors. In our meta-analysis, males showed higher all-cause and TB-related mortality and higher sputum culture and smear positivity rates during and after TB treatment.

Lengthy tuberculosis (TB) treatment is required to overcome the ability of a subpopulation of persistent Mycobacterium tuberculosis (Mtb) to remain in a non-replicating, antibiotic-tolerant state characterized by metabolic remodeling, including induction of the Rel Mtb -mediated stringent response. We developed a novel therapeutic DNA vaccine containing a fusion of the rel Mtb gene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3a/CCL20. To augment mucosal immune responses, intranasal delivery was also evaluated. We found that intramuscular delivery of the MIP-3a/rel Mtb (fusion) vaccine or intranasal delivery of the rel Mtb (nonfusion) vaccine potentiate isoniazid activity more than intramuscular delivery of the DNA vaccine expressing rel Mtb alone in a chronic TB mouse model (absolute reduction of Mtb burden: 0.63 log 10 and 0.5 log 10 colony-forming units, respectively; P=0.0002 and P=0.0052), inducing pronounced Mtbprotective immune signatures. The combined approach involving intranasal delivery of the DNA MIP-3a/rel Mtb fusion vaccine demonstrated the greatest mycobactericidal activity together with isoniazid when compared to each approach alone (absolute reduction of Mtb burden: 1.13 log 10 , when compared to the intramuscular vaccine targeting rel Mtb alone; P<0.0001), as well as robust systemic and local Th1 and Th17 responses. This DNA vaccination strategy may be a promising adjunctive approach combined with standard Frontiers in Immunology frontiersin.org 01