Factors Associated with 30-Day in-Hospital Mortality Among Patients Admitted with Severe Covid-19 in Mbarara Regional Referral Hospital

Andrew Mutekanga,1,&ast; Edwin Nuwagira,1,&ast; Elias Kumbakumba,2 Victoria Nyaiteera,3 Stephen Asiimwe,4 Medal Gasumuni,5 Nelson Wandera,5 Robert Natumanya,5 Denis Akena,5 Siraje Senoga,1 Joseph Kyobe Kiwanuka,6 George Kateregga,6 Emmanuel Munyarugero,6 Fardous Charles Abeya,1 Paul Stephen Obwoya,1 Stephen Ttendo,6 Rose Muhindo1,&ast; 1Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 2Department of Pediatrics and Child Health, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of ENT, Mbarara University of Science and Technology, Mbarara, Uganda; 4Global Health Collaborative, Massachusetts General Hospital, Boston, MA, USA; 5Department of Medicine, Mbarara Regional Referral Hospital, Mbarara, Uganda; 6Department of Anesthesiology and Critical Care, Mbarara University of Science and Technology, Mbarara, Uganda&ast;These authors contributed equally to this workCorrespondence: Rose Muhindo, Mbarara University of Science and Technology, P.O. Box 1410, Mbarara, Uganda, Tel +256772406337, Email [email protected]: COVID-19 has created a burden on the healthcare system globally. Severe COVID-19 is linked with high hospital mortality. Data regarding 30-day in-hospital mortality and its factors has not been explored in southwestern Uganda.Methods: We carried out a retrospective, single-center cohort study, and included all in-patients with laboratory-confirmed, radiological, or clinical severe COVID-19 admitted between April 2020 and September 2021 at Mbarara Regional Referral Hospital (MRRH). Demographic, laboratory, treatment, and clinical outcome data were extracted from patients’ files. These data were described comparing survivors and non-survivors. We used logistic regression to explore the factors associated with 30-day in-hospital mortality.Results: Of the 283 patients with severe COVID-19 admitted at MRRH COVID-19 unit, 58.1% were male. The mean age ± standard deviation (SD) was 61± 17.4 years; there were no differences in mean age between survivors and non-survivors (59 ± 17.2 versus 64.4 ± 17.3, respectively, p=0.24) The median length of hospital stay was 7 (IQR 3– 10) days (non-survivors had a shorter median length of stay 5 (IQR 2– 9) days compared to the survivors; 8 (IQR 5– 11) days, p< 0.001. The most frequent comorbidities were hypertension (30.5%) and diabetes mellitus (30%). The overall 30-day in-hospital mortality was 134 of 279 (48%) mortality rate of 47,350× 105 with a standard error of 2.99%. The factors associated with 30-day in-hospital mortality were age: 65 years and above (aOR, 3.88; 95% CI, 1.24– 11.70; P =0.020) a neutrophil to lymphocyte ratio above 5 (aOR, 4.83; 95% CI, 1.53– 15.28; P =0.007) and oxygen requirement ≥ 15L/min (aOR, 15.80; 95% CI, 5.17– 48.25; P < 0.001).Conclusion: We found a high 30-day in-hospital mortality among patients with severe forms of COVID-19. The identified factors could help clinicians to identify patients with poor prognosis at an early stage of admission.Keywords: severe, COVID-19, 30-day in hospital mortalit

Respiratory Support Techniques for COVID-19-Related ARDS in a Sub-Saharan African Country: A Multicenter Observational Study.

BACKGROUND: Few data from low-income countries report on respiratory support techniques in COVID-19-associated ARDS. RESEARCH QUESTION: Which respiratory support techniques are used in patients with COVID-19-associated ARDS in Uganda? STUDY DESIGN AND METHODS: A multicenter, prospective, observational study was conducted at 13 Ugandan hospitals during the pandemic and included adults with COVID-19-associated ARDS. Patient characteristics, clinical and laboratory data, initial and most advanced respiratory support techniques, and 28-day mortality were recorded. Standard tests, log-rank tests, and logistic regression analyses were used for statistical analyses. RESULTS: Four hundred ninety-nine patients with COVID-19-associated ARDS (mild, n = 137; moderate, n = 247; and severe, n = 115) were included (ICU admission, 38.9%). Standard oxygen therapy (SOX), high-flow nasal oxygen (HFNO), CPAP, noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) was used as the first-line (most advanced) respiratory support technique in 37.3% (35.3%), 10% (9.4%), 11.6% (4.8%), 23.4% (14.4%), and 17.6% (36.6%) of patients, respectively. The first-line respiratory support technique was escalated in 19.8% of patients. Twenty-eight-day mortality was 51.9% (mild ARDS, 13.1%; moderate ARDS, 62.3%; severe ARDS, 75.7%; P < .001) and was associated with respiratory support techniques as follows: SOX, 19.9%; HFNO, 31.9%; CPAP, 58.3%; NIV 61.1%; and IMV, 83.9% (P < .001). Proning was used in 79 patients (15.8%; 59/79 awake) and was associated with lower mortality (40.5% vs 54%; P = .03). The oxygen saturation to Fio2 ratio (OR, 0.99; 95% CI, 0.98-0.99; P < .001) and respiratory rate (OR, 1.07; 95% CI, 1.03-1.12; P = .002) at admission and NIV (OR, 6.31; 95% CI, 2.29-17.37; P < .001) or IMV (OR, 8.08; 95% CI, 3.52-18.57; P < .001) use were independent risk factors for death. INTERPRETATION: SOX, HFNO, CPAP, NIV, and IMV were used as respiratory support techniques in patients with COVID-19-associated ARDS in Uganda. Although these data are observational, they suggest that the use of SOX and HFNO therapy as well as awake proning are associated with a lower mortality resulting from COVID-19-associated ARDS in a resource-limited setting

COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase

Abstract Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we profile the peripheral blood proteome and transcriptome to characterize the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures are generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scale with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 is distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8+ T cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe acute respiratory infections, we show that activation of epidermal and platelet-derived growth factor pathways are distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity