In this first retrospective cohort study from Niger, we report the phenotype of patients hospitalized for COVID-19 suspicion, predictors associated with the odds of respiratory symptoms and predictors associated with the hazards of death among those who tested positive for COVID-19. We found that predictors independently associated with in-hospital mortality in relation to COVID-19 infection were age (mainly 60 years or older), history of comorbidity and baseline shortness of breath.
Socio-demographic and clinical parameters linked to the severity and mortality of COVID-19 have been widely reviewed [11,12,13,14,15]. Age is considered to be strongly correlated with COVID-19 outcomes globally [14, 16], but little is known about the situation on the African continent. A recent systematic review (n = 15 studies) reported that elderly adults and people with comorbidities suffer severe forms of COVID-19 and are at increased risk of hospitalization and death [17]. We found that patients hospitalized with a suspected COVID-19 infection who remained negative for SARS-CoV-2 were significantly younger than those who tested positive for SARS-CoV-2, as well as those who died. In addition, we found that every increase in year of age, was significantly associated with higher odds of reporting cough or fever/chills but was associated with a slightly reduced in risk of reporting rhinorrhea. Humans have developed natural immunity and immunological memory to withstand repeated infections. However, dysregulated adaptative immunity associated with the ageing process is known to increase the risk of morbidity following a decline in the immune system [18]. For example, roughly 90% of the excess deaths for seasonal influenza happen in elderly people. There is progressive lymphopenia with CD4 + T-cell attrition in the aging immune system, and reduced regulatory T-cell activity that contribute to homeostatic proliferation of lymphocytes with autoimmune tendency and unnecessary inflammatory responses [19]. Lymphopenia is a hallmark of SARS-CoV-2 infection [20] and is affected by several variables such as those that impact survival. Infection, such as with COVID-19, then exacerbates the imbalanced aged immune system, thereby exacerbating the loss of CD4 + T cells and inflammatory macrophage reaction [19].
In agreement with our findings, a study of 1028 confirmed cases of COVID-19 from Africa has also identified chronic diseases as an independent factor associated with death among patients infected with SARS-CoV-2 [21]. Chronic conditions are often associated with a sub-clinical level of inflammation, weakened innate immune responses and a strong ACE-2 receptor facilitating SARS-CoV-2 entry into the host cells [11, 13]; and correlating with COVID-19 severity [22]. These comorbidities carry the COVID-19 patient through a vicious infectious life cycle (amplification of cytokine storm) and are significantly correlated with severe morbidity and mortality [13, 23]. In our cohort, a history of comorbidity was common and more prevalent among those who tested positive for COVID-19; cardiometabolic diseases (cardiovascular diseases, hypertension, and diabetes) and chronic respiratory illnesses (COPD and asthma) were the most frequently reported. This is in line with previous data [24] (participants, n = 202,005 patients with COVID-19) showing any type of chronic comorbidity, hypertension/cardiovascular disease, diabetes, and respiratory diseases were the most prevalent chronic comorbid conditions. As in our study, polymorbidity was also common. However, the extent to which comorbidities influence the pandemic remains questionable. Previous research synthesis have shown some methodological limitations by using preprint data and limited global clinical data [11, 25]. A more recent meta-analysis of published data from large cohorts from across the world reported that hypertension, diabetes, and cancer significantly exacerbate the severity of COVID-19 in patients resulting in death, however, chronic kidney diseases contributed the most to death [11]. Analyzing the association between chronic comorbidity and COVID-19 severity/fatality by country of residence, Zhou et al. found that such odds were highly and significantly increased for obesity in France (compared to that in USA, UK and China), for hypertension/ cardiovascular diseases in China and for diabetes in the USA [26]. HIV-infection and/or tuberculosis independently predicted the hazard of death in South Africa [12] and of severity in Ethiopia [27], but not in studies from the USA [15, 28]. As such, the call by The African Forum for Research and Education in Health [6, 7] to pool COVID-19 data from African countries very necessary to enhance COVID-19 epidemiology in Africa to ensure an adaptive response at both hospital and community levels.
COVID-19 typical symptoms include fever, cough and shortness of breath [29,30,31,32]. The most frequent symptoms reported in our cohort were cough, fever/chills and shortness of breath with half of patients who died exhibiting fever/chills and/ or shortness of breath at presentation. Furthermore, shortness of breath was also a predictor of death. Latest evidence indicate that a number of patients with serious COVID-19 might have the cytokine storm syndrome [23]. The cytokine storm syndrome might explain COVID-19-related clinical symptoms and signs such as fever, cough/sputum, shortness of breath, faster respiratory rates, stuffy nose and generalized malaise, as these are common to other diseases-associated cytokine storm syndrome [33]. However, shortness of breath (regardless of degree of severity) has been identified as critically important core outcomes by more than 9,300 patients, health professionals, and the public from 111 countries in the global Coronavirus Disease 2019 Core Outcome Set Initiative [34]. This is important since it will help to capture the dynamic nature of COVID-19, illustrate the debilitating severity, and measure the progress in the resumption of daily activities. The congestion of the intensive care unit can be correlated with the fatality of COVID-19 [35]. Prioritizing patients in need of intensive treatment is required to reduce the death rate during the pandemic [36]. Therefore, knowing the predictive potential of baseline symptoms in a deadly pandemic is particularly valuable in settings with resource shortages, such as rural Africa. In agreement with many prognosis scores simply excluding laboratory/imagery data (machine learning model or not), shortness of breath/ dyspnea significantly predicted COVID-19 severity (hospitalization, stay in intensive care and or death) [8, 35, 36]. Moreover, in one model, laboratory data only predicted clinical deterioration while baseline clinical data such age and shortness of breath/ dyspnea significantly predicted the hazards of death among critically ill patients [37].
Although informative, our research highlights the need to design prospective studies to address the identified shortfalls. The use of registry-based data designed at the onset of the pandemic (at risk of missing data) is one of the main shortcomings of our research. This did not allow us to provide a full understanding of comorbidity (e.g., very low prevalence of reported obesity and HIV) and, as a result, we did not include each comorbidity in the updated models to prevent misleading interpretation. Similarly, roughly 2% of patients hospitalized for COVID-19 missed final clinical outcome but no difference was observed for other baseline characteristics compared to included patients. Moreover, COVID-19 clinical severity, laboratory and imaging results were not routinely recorded in the national public health record and were consequently not included in this first study. Although one might assume that hospitalized patients were more likely to present with moderate to severe COVID-19 stage we also acknowledge that not considering this information might bias our findings either away, or towards the true effect. However, our research included a comprehensive data from all eight provinces in Niger and thus offered a thorough real-world description of COVID-19 epidemiology in this humanitarian setting. Moreover, while this is the first report from Niger, we are also the first to compare the variation in clinical features among all hospitalized patients quarantined for COVID-19 infection, considering this region has the highest burden of other respiratory diseases in Africa.
