Factors Associated with Cardiovascular Complications and Mortality in Patients with Covid-19 Treated at Care Sites in Benin between 2020 and 2021

  

    
 
    
Univariate
    
 
    
 
    
Multivariate
    
 
  
  

    
ORb    [CI 95%]
    
P-value
    
ORa    [CI 95%]
    
P    value
  
  

    
Age (years)
    
 
    
< 0.001
    
 
    
 
    
0.702
  
  

    
< 50
    
1
    
 
    
 
    
1
    
 
  
  

    
≥ 50
    
1.18[1.12-1.24]
    
 
    
 
    
1.09[0.69-1.69]
    
 
  
  

    
Type of cases
    
 
    
< 0.001
    
 
    
 
    
<    0.001
  
  

    
Simple
    
1 
    
 
    
 
    
1
    
 
  
  

    
Moderate
    
2.50 [0.97-6.42] 
    
 
    
 
    
1.03 [1.03-62.43]
    
 
  
  

    
Severe 1
    
19.42 [8.23-45.82] 
    
 
    
 
    
23.52 [3.11-177.76]
    
 
  
  

    
Severe 2
    
38.62 [16.37-91.12] 
    
 
    
 
    
106.31 [14.50-779.74]
    
 
  
  

    
Severe 3
    
53.60 [22.65-126.86] 
    
 
    
 
    
448.67 [61.24-3287.40]
    
 
  
  

    
Cancer
    
 
    
0.607
    
 
    
 
    
0.012
  
  

    
Yes
    
0.75 [0.26-2.22] 
    
 
    
 
    
3.81 [1.35-10.76]
    
 
  
  

    
No
    
1 
    
 
    
 
    
1
    
 
  
  

    
Chronic renal failure
    
 
    
< 0.001
    
 
    
 
    
<    0.001
  
  

    
Yes
    
3.60 [2.75-4.70] 
    
 
    
 
    
8.00 [4.00-15.99]
    
 
  
  

    
No
    
1 
    
 
    
 
    
1
    
 
  
  

    
Decompensation of a    pre-existing heart disease 
    
 
    
< 0.001
    
 
    
 
    
< 0.001 
  
  

    
Yes
    
3.28 [2.03-5.30] 
    
 
    
 
    
4.11 [1.27-13.35]
    
 
  
  

    
No
    
1 
    
 
    
 
    
1
    
 
  

Table 4: Factors associated with death from COVID-19 in patients hospitalized at the three Epidemic Treatment Centres in Benin during the period from March 16,
2020 to June 31, 2021 (N=1265).

Discussion

This study was initiated to assess cardiovascular morbidity and mortality among patients with COVID-19 hospitalised and treated in Benin. Taking into account all the cases received in the three ETCs in Benin, we believe that our sample is representative of the cases of COVID-19 treated in hospital settings in Benin. Indeed, at the advent of the COVID-19 pandemic, Benin took the option of gathering all cases requiring hospital care in three ETCs created for this purpose. Thus, all cases of COVID-19 are systematically referred to one of these ETCs. The ETC of Parakou takes into account cases from the North region, the one of Allada takes cases from the Centre and the South and the ETC of Cotonou, cases from the South.

These ETCs are led by a multidisciplinary medical team made up of resuscitators, cardiologists, infectiologists and general practitioners who are present there on a permanent basis. When necessary, other medical specialists intervene to give advice. In order to refine the diagnoses and the therapeutic decisions of the cases managed on these sites, a national staff is set up and meets three times a week through the Microsoft Teams software. During these staff meetings, other national and international specialists give their opinions on the management of each patient. All of these precautions guarantee the quality of the data we have collected from the patients’ medical files.

At the end of this work, we observed that 22.7% of patients had at least one cardiovascular risk factor. Pulmonary embolism, heart failure and arrhythmia were the main cardiovascular manifestations presented by patients during COVID-19. The mortality rate was 16.5%. Case severity, cancer, chronic renal failure and decompensation of a pre-existing heart disease were the predictors of death among patients hospitalized for COVID-19 in Benin. Although COVID-19 is a recent disease, the speed of its spread and its lethality have prompted the publication of a multitude of data from different regions of the world. It is therefore necessary to analyse the Beninese situation in relation to this rich literature.

The Age of the Patients

In our study, the median age of the patients was 51 years (35; 64).; Grasselli et al. in Italy in 2020 observed a higher mean age of 63 years [11]. This age difference could be explained by the fact that the life expectancy of the Italian population is higher than that of Africa.

Pre-Existing Cardiovascular Risk Factors and Diseases

Arterial hypertension is the most common cardiovascular risk factor in our study, found in 45.2% of cases. This history of hypertension was observed in 49% of patients in Italy in 2020 [11], and 37.2% of cases in China the same year [12].

Diabetes was found in 24.3% of patients. This frequency is similar to that of Du et al., and Huang et al. in China in 2020, which were respectively 22.4% and 20% [12,13]. Diabetes is thus, the second most common cardiovascular risk factor after hypertension in patients hospitalized for COVD-19.

The history of stroke was reported in 5.5% of our patients. This observation corroborates the 5.3% found by Shi et al. in China in 2020 [14] and the 5.1% found by Zhou et al. in the same country, and during the same year [15].

Concerning pre-existing heart diseases, they were found in 4.4% of patients. This frequency is similar to the 4.3% published by Guo et al. in China in 2020 [16], but lower than the 9.7% reported by Kumar et al. in India in 2020 [17]. This difference could be explained by their larger sample sizes, but also by the disparity of the diagnostic tools available depending on the setting. Indeed, the cardiology technical platform in Benin is sparse and the exploration of heart disease is limited to clinic examination, electrocardiogram and cardiac echo- Doppler. Thus, some asymptomatic heart diseases go unnoticed and only reveal themselves when complications or other acute illnesses occur [18]. This usually unrecognized cardiovascular background often affects the evolution of intercurrent conditions such as COVID-19 [16,19,20].

The Evolution of Patients with COVID-19

At the end of our study, the clinical recovery rate was 83.5%. This frequency is higher than the 71% and 77% respectively found by Zhou et al. and Guo et al. in China in 2020 [15,16]. This difference could be explained by the fact that the majority of patients admitted to intensive care in their studies had died compared to our study. Also, the fact that the proportion of severe cases in their studies was higher than ours. Indeed, in our study, severe COVID-19 cases were found in 46.4% of patients, against 62.3% found in the series of Zhou et al.

Frequency of Cardiovascular Complications and Mortality

Cardiovascular complications were present in 20.1% of patients. Pulmonary embolism ranked first with a frequency of 16.6%. Planquette et al. in France [21] and Whyte et al. in England [22] in 2020 reported lower frequencies than ours; 5.6% and 5.4% of cases respectively. This disparity could be explained by the systematic non-confirmation by CT angiography of some of our cases which unfortunately remain suspected cases of pulmonary embolism. In fact, the respiratory symptoms that constitute the main warning signs of pulmonary embolism were also the key manifestations of COVID-19 [23,24]. Only a multislice pulmonary CT angiography could provide diagnostic accuracy [7,8,24]. Unfortunately, this examination was not permanently available during the study period.

The pathogenic mechanisms involved in cardiovascular damage are multiple and make it possible to understand the frequent association between COVID-19 and pulmonary embolism. Indeed, the COVID-19 virus is responsible for hyper-inflammation accounting for diffuse activation of coagulation, both in the arterial and venous beds [26]. Faced with most situations of respiratory distress and strong clinical suspicion, the patients in our series received substantial anticoagulant treatment in case of impossibility to confirm pulmonary embolism. The cases, related to the severity of the infectious or inflammatory involvement of the lung parenchyma and not to the thromboembolism complications, might have been detected if angioscan had been systematically performed [7].

Heart failure was found in 3.2% of patients during their hospitalization and was more frequent in patients with advanced age. Wang L et al. [27] and Zhou et al. [15] in China in 2020 found significantly higher frequencies of 17.4% and 23% respectively. This difference could be explained by the high proportion of patients with underlying heart disease in their studies. Indeed, the presence of heart disease was found in 4.4% of patients in our study. This proportion is lower than the 15.7% found by Wang L et al. Patients with preexisting heart disease are at higher risk of developing heart failure from COVID-19, which is a decompensating factor.

The mortality rate was 16.5% in our study. This rate is close to the 19% and 20.3% found by Wang L et al. in China in 2020 [27] and Rosenthal et al. in the United States in 2020 [28]. Ferrando et al. in Spain in 2020, on the other hand, found a rate of 31% [29]; this high frequency could be explained by the inclusion of patients only in intensive care in their studies, therefore cases of extreme severity or involving several damages.

Risk Factors for Death of Patients with COVID-19 in Benin between 2020 and 2021

After multivariate analysis, the factors associated with death among patients hospitalized for COVID-19 were; the severity of the case (CI [3.11-3287.40]; p< 0.001); the co-existence of cancer (ORa 3.81; CI [1.35-10.76]; p=0.012), chronic renal failure (ORa 8.00; CI [4.00-15.99]; p< 0.001) and the decompensation of pre-existing heart disease (ORa 4.11; CI [1.27-13.35]; p=0.019). Other studies have found risk factors different from those found in our study. Zhou et al. in China in 2020 found in multivariate analysis that risk factors of mortality were; older age (CI [1.03-1.17]; p = 0.0043), a high SOFA (Sepsis Organ Failure Assessment) score (CI [2.61-12.23]; p <0.0001) and D-dimers greater than 1 g/ml on admission (CI [2.64-128.55]; p = 0.0033) [15]. Rosenthal et al. in the United States in 2020 found in multivariate analysis that advanced age was the risk factor most strongly associated with mortality (P < 0.001). The risks of death were 16.2 times higher in hospitalized patients aged 80 years or older, than in those aged 18-34 years (age ≥ 80 years vs 18-34 years: odds ratio [OR], 16.20 95% CI, 11.58-22.67; P < 0.001) [28]. Ouedraogo et al. in Burkina Faso in 2020 also found advanced age (age ≥ 65 years) (HR: 2.3; CI (1.2-4.3); p=0.011) as a risk factor for death [30]. This difference compared to the factors found in our study could be explained on one hand by the fact that our patients are of younger age and on the other hand by the availability of D-dimers in the screening of patients from the day of admission in the study by Zhou et al [15].

Limits and Weaknesses of the Study

Due to the retrospective nature of this work, some data, particularly the one on the evolution of patients, were not found in all of the files, which did not allow a precise analysis, thus reducing the power of our results. Also, the lack of systematic performance of some of the paraclinical examinations in certain clinical situations may have contributed to the underestimation of some cardiovascular complications of COVID-19. For example, D-Dimers or CT angiography were not performed in certain patients with suspicious signs of pulmonary embolism. Similarly, the dosage of troponins I in the presence of suspected myocarditis and acute coronary syndrome and the coronary angiography and cardiac MRI were not systematic.

Thus, the diagnosis of acute coronary syndromes and myocarditis remains imprecise [31,32]. These common complications of COVID-19 are then, probably underestimated in our work.

Despite these limitations, this study provided important data on COVID-19 and cardiovascular disease in a low-income country like Benin.

Conclusion

The evolution of patients with COVID-19 is burdened with significant mortality, but also influenced by the presence of risk factors and/or pre-existing cardiovascular conditions, and/or direct cardiovascular manifestations due to this disease. This study identified factors associated with cardiovascular complications and death in patients with COVID-19 in Benin.

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