key: cord-0727159-f3r5aitk
authors: Ebongue, Marie Solange Ndom; Lemogoum, Daniel; Endale-Mangamba, Laurent Mireille; Barche, Blaise; Eyoum, Christian; Simo Yomi, Styve Hermane; Mekolo, David; Ngambi, Vincent; Doumbe, Jacques; Sike, Christiane Medi; Boombhi, Jerome; Ngondi, Grace; Biholong, Christian; Kamdem, Josephine; Mbenoun, Liliane; Tegeu, Calixthe Kuaté; Djomou, Armel; Dzudie, Anastase; Kamdem, Felicité; Ntock, Ferdinand Ndom; Mfeukeu, Liliane Kuaté; Sobngwi, Eugène; Penda, Ida; Njock, Richard; Essomba, Noel; Yombi, Jean Cyr; Ngatchou, William
title: Factors predicting in-hospital all-cause mortality in COVID 19 patients at the Laquintinie Hospital Douala, Cameroon
date: 2022-03-18
journal: Travel Med Infect Dis
DOI: 10.1016/j.tmaid.2022.102292
sha: 582d1200806b68d51604cd6d43fb2adce8fac351
doc_id: 727159
cord_uid: f3r5aitk

BACKGROUND: Despite being a global pandemic, little is known about the factors influencing in-hospital mortality of COVID-19 patients in sub-Saharan Africa. This study aimed to provide data on in-hospital mortality among COVID-19 patients hospitalized in a single large center in Cameroon. METHODS: A hospital-based prospective follow-up was conducted from March 18 to June 30, 2020, including patients >18 years with positive PCR for SARS-COV-2 on nasopharyngeal swab admitted to the Laquintinie Douala hospital COVID unit. Predictors of in-hospital mortality were assessed using Kaplan Meir survival curves and Weibull regression for the accelerated time failure model. Statistical significance was considered as p < 0.05. RESULTS: Overall 712 patients (65,7% men) were included, mean age 52,80 ± 14,09 years. There were 580 (67,8% men) in-hospital patients. The median duration of hospital stay was eight days. The in-hospital mortality was 22.2%. Deceased patients compared to survivors were significantly older, had a higher temperature, respiratory rate, and heart rate, and lowest peripheral oxygen saturation at admission. After adjusting for age, sex, and other clinical patient characteristics, increased heart rate, increased temperature, decreased peripheral oxygen saturation. The critical clinical status was significantly associated with increased in-hospital mortality. In contrast, hospitalization duration greater than eight days and the use of hydroxychloroquine (HCQ) + azithromycin (AZM) therapy was associated with decreased risk of in-hospital mortality. CONCLUSION: One in five hospitalized COVID-19 patients die in a low-middle income setting. Critical clinical status, dyspnea, and increased heart rate were predictors of in-hospital mortality. This study will serve as a prerequisite for more robust subsequent follow-up studies. Also, these results will aid in revising national guidelines for the management of COVID-19 in Cameroon.

The world is experiencing an unprecedented pandemic of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, Hubei province, China. As of January 19, 2021, according to the World Health Organization (WHO) estimates, more than 96 million people have been infected worldwide, with more than 2000000 deaths. 1 Studies carried out in Europe, North America, and Asia seem to show that in a substantial minority of patients, COVID-19 can be severe, with particularly high fatality rates among older people (>65 years) and in those with certain common comorbid conditions, such as cardiovascular diseases (CVD), chronic pulmonary disease, chronic kidney disease (CKD), archaic genetic variants (in Eurasians), inborn errors or auto-antibodies interfering with interferon of immunity and cancer, but also cardiovascular risk factors (CVRFs) such as diabetes, hypertension, and obesity. 2, 3, 4, 5, 6 While the pathophysiology of COVID-19 remains incompletely understood, patients can develop severe acute respiratory distress syndrome (ARDS), but also shock, thrombosis, and multiple organ failure. 2, 3 Mortality rates for patients admitted to intensive care units are as high as 22%, 7 in China and 26% in Italy during the first wave. 8 Though there is an increased burden of several non-communicable diseases in sub-Saharan Africa (SSA) compared to other regions of the world, the African continent overall presents the lowest mortality rate, albeit this can be attributed to the low test per case ratio 9, 10 . A large cohort study in South Africa (SA) suggests that risk factors such as gender, age, hypertension, diabetes, HIV, and tuberculosis were associated with COVID-19 outcome. 11 Furthermore, critical or severe COVID-19 and dyspnea on admission were potential predictors of mortality in the SSA setting 12 . Although a couple of studies have explored factors associated with 15mg twice daily while enoxaparin was given 1 IU/Kg/12h. We used prednisolone 20mg twice a day or methylprednisolone 40mg/8h IV in critically ill patients regarding corticoids.

This study was conducted following the declaration of Helsinki. Ethical clearance was obtained from the LHD institutional review board, whereas administrative clearance was obtained from the Regional Delegation of Public Health for the Littoral Region.

Patients' age, sex, comorbidities, smoking status, symptoms, vitals signs at admission, treatment received, and outcomes were collected from all patients. Variables were defined as follow: Heart rate /min (normal: 60-100, abnormal: < 60 & >100, Tachycardia >100);

Respiratory rate /min (normal:12-20, abnormal <12 or >20); peripheral oxygen saturation (normal >96%, abnormal ≤ 96%); Temperature °C (normal: 36,5° -37,5°, abnormal : 

Overall there were 712 patients (65,69% men) with laboratory-confirmed COVID-19, of which, 580 (67,8% men) were hospitalized and 132 (56,06% women) were followed as outpatients. The mean age of hospitalized cases was 52.88(14.22) years. Survivors were younger than patients who died. Also, the prevalence of diabetes was significantly higher in patients who died.

In addition, deceased patients presented with higher body temperature, respiratory rate, and resting heart rate; similarly, deceased patients presented lower peripheral oxygen saturation at baseline. The most common clinical presentations were cough, fever, and dyspnea. Survivors were less likely to present with dyspnea The median duration of hospitalization was 8 days, and deceased patients had a shorter duration of hospital stay. The in-hospital all-cause mortality was 22.2% and was comparable between males and females. A linear trend of increasing mortality was observed from the lowest to the highest age quartile. Table 1 summarizes the baseline characteristics of study participants by mortality status J o u r n a l P r e -p r o o f

There was an increased risk of mortality from mild through critical clinical status (log-rank < 0.01) (Figure 2 ). For every 10 year increase in age, the risk of in-hospital mortality increased by 36%, and this effect was persistent in multivariable analysis (adjusted Hazards Ratio (1.28, [1.09-1.49], p< 0.01). Increased body temperature, heart rate, respiratory rate, and decreased peripheral oxygen saturation at baseline were associated with increased risk of in-hospital mortality. However, the increased respiratory rate was not significant after adjusting for age, sex, and other comorbidities. Dyspnea at baseline increased the crude risk of mortality by 767%; however, this was not significant in the multivariable analysis (aHR 2. Table 2 summarizes the results obtained from univariable and multivariable Weibull regression analysis.

In this first large prospective observational study of hospitalized patients with COVID-19 in Cameroon, we found an in-hospital mortality rate of 22,2% due to the severe clinical status J o u r n a l P r e -p r o o f before admission. These results will be relevant in public health decision-making and in improving the care of COVID 19 patients in SSA 14 . Indeed, knowledge of these mortality figures could remind the population that this pathology is not benign and that preventive measures must continue to be applied. The mortality rates in hospitalized patients reported previously range from 4 to 28% 3,15-17 in developed countries and 29% in the SSA setting 12 . In the latter study, 56% of patients arrived in a critical condition, and 70% of deaths occurred within the first 24 hours of admission, demonstrating the severity of the cases and probably the late arrival of patients at the hospital. In our study, 93% of the patients who died were in a severe or critical clinical status on arrival. In addition, the presence of dyspnea and critical clinical state on admission were the main factors associated with in-hospital mortality.

Although the ICU admission was not a factor associated with death after adjustment in the present study, these results show that it is important to treat patients early before they reach serious stages of the disease in our context where the hospital facilities are often insufficient to manage such patients 18 . Furthermore, the ICU mortality rate of 49% in our study remains higher than the average of 25.7% reported in the emerging literature 19

This study identified diabetes as a factor associated with in-hospital mortality in the univariate analysis. On the contrary, other chronic conditions such as hypertension, obesity, smoking, chronic kidney disease, HIV infection, and cancer did not affect hospital mortality. In South Africa, for example, COVID-19 mortality was independently associated with HIV and tuberculosis infection 11 whereas, in Kinshasa, hypertension and diabetes emerged as a chronic conditions independently associated with hospital mortality 12 .

Previously, older age has been reported as an important risk factor of death in COVID-19 disease. Our findings confirmed an increased risk of mortality for every 10-year increase in age. In developed countries, older age emerged as a strong mortality risk factor that can increase the risk by 30 fold for age groups over 80 years old 7, 16, 20 . In DRC, with a similar age J o u r n a l P r e -p r o o f pyramid, the non-survivors were older, and the risk of in-hospital death was increased 12 .

Several clinical signs and symptoms such as dyspnea, increased temperature, increased heart rate, already described previously as risk factors for increased mortality, were found in our study. We also noted that prolonged duration of hospitalization was associated with a lower risk of in-hospital mortality; this can have implications on the number of hospital beds and equipment available to continue care of new cases of Covid 19 and thus indirectly worsening outcomes in emerging cases.

To date, there is no effective treatment for COVID-19. Still, the ICU mortality has decreased substantially over time, possibly due to better hospital case management, including better ventilation practices and potentially effective treatments. 21 Treatment regimens such as the association of hydroxychloroquine and azithromycin are extensively used in Africa despite controversies on the efficacity and cardiovascular safety. 22, 23 The combination of hydroxychloroquine and azithromycin demonstrated a significantly reduced risk of in-hospital mortality in this study, similar to the reports in some studies 24 .

However, these results have been contrasted by several studies [25] [26] [27] . This difference can be explained by the absence of randomization in our study. Also, it shall be noted that patients who received hydroxychloroquine and azithromycin combination were younger had higher peripheral oxygen saturation. Moreover, a relatively lower proportion of patients on hydroxychloroquine and azithromycin combination presented with a critical clinical status at baseline compared to their counterparts (16.7% vs. 41.5%)

Other medications such as corticosteroids and anticoagulants introduced in our treatment protocol six weeks after the beginning of this study did not impact hospital mortality in our study. However, the large randomized Recovery study has highlighted the benefits of glucocorticoids in the outcome of COVID-19 patients requiring oxygen. The lack of J o u r n a l P r e -p r o o f therapeutic efficacy of corticosteroids in our study could be explained by the delayed administration and the difference in the delivery modality in Cameroon.

This study has several limitations: firstly, the single-center approach limits the generalization of our results. Secondly, the late arrival of patients in the hospital could increase the number of severe cases admitted and therefore overestimate the overall mortality in our series. Also, given COVID 19 is a new disease with emerging literature, most of the patients in our cohort could have been exposed to different treatment protocols throughout recruitment.

Nevertheless, the substantial number of patients included in the present study and the scarcity of observational studies in our context makes this work useful for the scientific community 

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We acknowledge the efforts of every staff who worked in the covid unit during the study period.J o u r n a l P r e -p r o o f