key: cord-0772614-p6b9v4c2
authors: Chisale, Master R.O.; Nyambalo, Billy W.; Mitambo, Collins; Kumwenda, Pizga; Mwale, Saul E.; Mbakaya, Balwani Chingatichifwe
title: Comparative characterisation of Covid-19 patients with hypertension comorbidity in Malawi: A 1:2 Matched Retrospective Case Control Study
date: 2021-11-22
journal: IJID Regions
DOI: 10.1016/j.ijregi.2021.11.005
sha: b68aab2d6a663de6d72a3c49477a2fea65c48978
doc_id: 772614
cord_uid: p6b9v4c2

Objective The aim of this study was to characterize Covid-19 cases and explore risk factors associated with mortality among hypertensive patients with COVID-19 country-wide. Methods We used a retrospective case control study design to provide a detailed account of cases and explore risk factors associated with mortality among hypertensive patients with COVID-19 country-wide. A total of 441 patients were included in the study in the ratio of one case to two controls (1:2), matched by age. Results Deaths due to Covid-19 varied with hypertensive condition with more deaths registered in hypertensive patients. Clinical signs and symptoms in Covid-19 patients varied greatly between hypertensive and non-hypertensive patients, with a leaning favouring the latter. The risk of death due to Covid-19 among hypertensive patients increased with age and meaningfully associated with underlining comorbidities such as HIV, TB, cardiovascular, and liver disease. Conclusion Our study reveals predictive factors for mortality in COVID-19 hypertensive patients that can be used by policy makers and health care practioners to identify those at a higher risk and determine proper treatment approach to achieve best possible clinical outcomes.

In February 2020, the World Health Organization (WHO) designated the name Coronavirus disease-2019 to a clinical condition caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (WHO, 2020) . In the Malawian context, the first case was confirmed on 2 nd April, 2020 in Lilongwe and more cases and deaths followed over time (Chibwana et al., 2020; Chisale, Eric, Nyambalo, Chavura, & Mbakaya, 2021) .

According to UNICEF situation report, as of 13 th January 2021, Malawi had registered 9,991 cases of COVID19 including 275 deaths. Of these cases, 1,844 were imported infections and 8,147 were locally transmitted (UNICEF Malawi, 2021) . In Wuhan, China, old age, chronic major comorbidity, and male sex have consistently been associated with increased mortality (Chen et al., 2020) . Hypertension has been reported as the most common comorbidity for patients with Covid-19, which results in cases with more severe symptoms and higher mortality (Wang et al., 2021) .

In a study conducted in China, out of 20,982 patients with Covid-19, 12.6% suffered from hypertension, and was the most frequent coexisting condition . In the same study, it is reported that among patients who die of Covid-19, those with hypertension ranged from 6.0%-36% . Besides old age, male gender, respiratory diseases and diabetes, cardiovascular diseases such as hypertension is reported to be a strong predictor of worse clinical outcomes in COVID-19 patients .

In Malawi, as of 31 st January, 2021, 23,963 people had been infected with COVID-19 pandemic country-wide (Ministry of Health Malawi, 2021; Worldometer, 2021) , with 1,017 admissions and 345 deaths. However, there is paucity of country-wide data on the outcomes of hypertensive hospitalized patients with COVID-19 in Malawi. Furthermore, predictors of mortality among hypertensive patients with Covid-19 are unknown. The aim of this study was to characterize Covid-19 cases and explore risk factors associated with mortality among hypertensive patients with COVID-19 country-wide.

This study used a retrospective case control study design. The focus was on all complete records ministry of health across the country for covid-19 patients with hypertension and their controls in the ratio of 1:2 matched by age. Increasing a ratio of one case to two controls, helped to increase the power of the study (Stürmer T, 2001) . In addition, matching the cases to controls by age, helped to reduce the confounder, as hypertension is directly proportional to advancements in age (Lenfant, 1990) .

This study included all patients records of those who had COVID-19 and hypertension in Malawi between 6 th April 2020 and 31 st January 2021 as cases. On the other hand, controls comprised of Covid-19 patients without hypertension within the same specified time period as cases. Epidemiological data, and clinical data including chronic illnesses were extracted from the medical registry/case file and nationally designed line listing (See supplementary documents) (ref…..). This study used census approach to identify cases, as all cases (hypertensive Covid-19 patients) were included. A systematic random sampling technique was used to select controls (Covid-19 patients without hypertension).

A total of 441 patients were included in the study with 145 cases and 296 controls, matched by age in a ratio of 1:2 (See Figure 1) .

A case was any Covid-19 patient who had a known and confirmed hypertensive condition, while a control was any Covid-19 patient without hypertension, as inclusion criteria. We excluded all incomplete records.

A diagnosis of hypertension was confirmed by a qualified clinician and documented in the patient's file and health passport. For both cases and controls, the SARS-CoV-2 infection was confirmed by RT-PCR using swab samples from the upper respiratory tract (nasopharyngeal/oropharyngeal), from the lower respiratory tract (sputum/endotracheal aspirate). Tests were carried out with the Abbott m2000 SARS-CoV-2 Real Time PCR Detection Kit.

Ethical approval to conduct this study was obtained from the National Health Science

Research Committee (NHSRC) (Protocol # NHSRC20/11/2630). Clearance was obtained from authorities from Ministry of Health. No name or any other identifiable information for the patients was indicated on the data collection form which authors adapted from Ministry of Health. Data was extracted from the medical files/forms by research assistants who were trained for three days prior to data collection.

Data was analysed using the Statistical Product and Service Solutions (SPSS) version 25.0.

(SPSS Inc., Chicago, IL, USA). Quantitative variables were expressed as mean ± standard deviation while qualitative variables were expressed as frequencies and percentages. A nonparametric test employing a Mann Whitney U-test was utilized to compare quantitative variables between hypertensive and non-hypertensive groups. The chi-square test was used to evaluate categorical data. A posthoc test employing a Bonferroni method was applied to the p-values obtained from chi-square test performed on different categorical variables Multivariable Cox regression analyses was used to investigate the risk factors associated with Covid-19 deaths. P-value was considered significant at p < 0.05

The mean age of all Covid-19 patients was 52.3(±15.6) and did not significantly vary between the hypertensive and non-hypertensive groups (See Table 1 ). The majority of Covid-19 patients were males (65.5%) (See Table 1 ). Hospitalization and mechanical ventilation requirements of Covid-19 cases was significantly higher among those with hypertension. In this study, more deaths were reported among Covid-19 cases with hypertension (17; n=21; p < 0.001). see Table 1 .

In this study, the reported signs and symptoms due to SARS-CoV-2 infection were loss of smell or taste, difficulty in breathing, stiff nose, sore throat, runny nose, chest pain, nausea, general body weakness, headache and abdominal pains. These clinical signs and symptoms among Covid-19 patients varied greatly between hypertensive and non-hypertensive groups with a favourable leaning towards the non-hypertensive. However, abdominal pains were significantly higher among Covid-19 patients with hypertension (See Table 2 ). Further, diabetes, HIV, Asthma and Tuberculosis were more prevalent among hypertensive Covid-19 patients ( Table 2 ). The Cox proportional hazard regression model results revealed that the risk of Covid-19 deaths among hypertensive patients increased with age and was meaningfully amplified by underlining comorbidities such as HIV, TB, cardiovascular, and liver disease were at higher risk of dying (Table 3 )

Despite several reports indicating the need for characterization of Covid-19 cases in particular settings (Chisale, Ramazanu, Wu, & Sinyiza, 2020; Master R O Chisale et al., 2021; Salyer et al., 2020; Vallverdu et al., 2021) , so far, there is no national wide comprehensive study on Malawian perspective on risk factors of COVID-19 patients with hypertension.

Furthermore, most of the published data are from Europe, Asia, America and other settings (Clark, Martin, & Clark, 2021; Hosseinzadeh, Ali, Beig, Bahardoust, & Alvanegh, 2021; Lavery et al., 2021; Shibata et al., 2020; Tadic, Saeed, Grassi, Taddei, & Mancia, 2021; Wang et al., 2021) making it unfeasible for African countries to formulate their policies and strategies for fighting the COVID-19 pandemic based on their local settings. This is a 1:2 case-control study matched by age comprising of 441 confirmed COVID-19, with 145 (32.9%) known hypertensive patients. In this study using national wide data, we compared the clinical and epidemiological characteristics of confirmed COVID-19 known hypertensive with non-hypertensive patients and established some important risk factors predictive for mortality among COVID-19 hypertensive patients.

The mean age of all Covid-19 patients included in this study was 52.3(±15.6) and as expected did not significantly vary between the hypertensive and non-hypertensive groups. The hypertensive condition favoured significantly those hospitalized, mechanically ventilated and deaths of COVID-19 cases. This is not surprising as most developing countries have a youthful population.

Studies from different settings have shown clinical parameters which are predictors of worse clinical outcomes in COVID-19 patients (Salyer et al., 2020; Vallverdu et al., 2021; Yin, Li, Ying, & Luo, 2021; Zhou et al., 2020) . Among other notable factors include, old age, male gender, cardiovascular diseases, respiratory diseases and diabetes to be related with severe COVID-19 . Initially, most studies were focused on descriptions of different comorbidities including the influence of various risk factors, susceptibility, severity and mortality of COVID-19 patients. However, recently, a few studies have been reporting on particular risk factors, and hypertension is one of the most reported risk factor (Clark et al., 2021; Hosseinzadeh et al., 2021; Shibata et al., 2020; Tadic et al., 2021; Wang et al., 2021) .

Unfortunately, none of these studies are from the African region. The findings from our study shows that loss of smell or taste, difficulty in breathing, stiff nose, sore throat, runny nose, chest pains, nausea, general body weakness, headache and abdominal pains are clinical signs and symptoms which varied significantly regardless of the hypertensive or non-hypertensive condition among Covid-19 patients. But with an exception of abdominal pains, which was highly prevalent among Covid-19 patients with hypertension. However, unlike in our findings, study from Iran by Ramin et.al. (2021) found that fever and shortness of breath was more prevalent among the covid-19 patients with hypertension (Hosseinzadeh et al., 2021) .

The disparity could be due to differences in the SARS-CoV-2 variants circulating in different regions of the world and population involved. Furthermore, the differences could also be due to the populations involved, hence the differences in the manifestations may somehow vary. Therefore, there is a need for each particular population to have a clear detail of the characteristics of their cases for proper policy formulations (Master R O Chisale et al., 2021; Salyer et al., 2020) .

Similar to other studies, the Covid-19 cases in hypertensive patients were significantly associated with diabetic condition. Likely this could be due to the fact that diabetes and hypertension are commonly related in their pathophysiology (Gesesew et al., 2021) . However, unlike most of the findings from other studies and reports (Clark et al., 2021; Hosseinzadeh et al., 2021; Shibata et al., 2020; Tadic et al., 2021; Wang et al., 2021) , our findings show that most patients with hypertension had HIV, Asthma and Tuberculosis. Much as this may need to be further investigated and confirmed as well as to understand the pathophysiological relationship, it is known fact that HIV/AIDS as well as TB are very common in developing countries hence more likely to be prevalent (Master R O Chisale et al., 2021) . Furthermore, HIV/AIDS is known to have an influence in the whole immune system as well as multiple systems of the body hence likely being the culprit.

This study has revealed that the risk of Covid-19 deaths among hypertensive patients increases with age and is meaningfully amplified by HIV, TB, cardiovascular, and liver disease. Some studies have equally shown that cardiovascular diseases pose a higher risk for the hypertensive patients to die if they are having COVID-19 (Hosseinzadeh et al., 2021; Wang et al., 2021) . However, so far, no study has indicated HIV and TB as risk factors for increasing mortality among hypertensive patients if they are infected with COVID-19. It is worrisome to learn that local programmes responsible for HIV and TB are reportedly critically affected by the COVID-19 posing more challenges for those with these comorbidities to suffer (Thekkur et al., 2021) . Therefore, Malawian authorities may need to consider these risk factors when handling COVID-19 cases with hypertension.

This study being case control of 1:2 matched by age, helped to prevent imbalance of known risk factor such as age and potential confounding. Consequently, reducing variability thereby increase efficiency.

However, the results of our study must be interpreted with caution because our study employed a retrospective design in which some terms were out of researcher's control.

This was likely the most critical challenge which made us not to include some more variables for analysis. In additions, this being a retrospective case-control study, was not capable to directly compute incidence, temporal relationship, and subject to selection bias for the controls. Furthermore, although the case-control was matched by age, the authors did not match by time. This may have a potential for bias because Covid-19 care might have improved with time. However, this being a country-wide Covid-19 data, it may portray a reflection and confirm the outcomes of COVID-19 infection in patients with hypertension in Malawi.

This study has revealed that the risk of Covid-19 deaths among hypertensive patients increases with age and is meaningfully amplified by HIV, TB, cardiovascular and liver disease. This study has characterized our local COVID-19 patients with hypertension so as to guide our local policies and efforts. Furthermore, our study reveals predictive factors for mortality in COVID-19 that can be used by health care practitioners to identify high risk hypertensive COVID-19 cases and determine proper treatment approach to achieve best possible clinical outcomes.

The data for the study are available from the corresponding authors on reasonable request.

The ethical approval to conduct the study was obtained from the National Health Science Research Committee (NHSRC), Protocol # NHSRC20/11/2630.

Written or oral informed consent was waived by the NHSRC. 

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan , China : a descriptive study

High SARS-CoV-2 seroprevalence in health care workers but relatively low numbers of deaths in urban Malawi

Community-based interventions for preventing COVID-19 transmission in low-and middle-income countries : A systematic review

COVID-19 and hypertension : risks and management . A scienti fi c statement on behalf of the British and Irish Hypertension Society

Risk factors for COVID-19 infection , disease severity and related deaths in Africa : a systematic review. 1-10

Should all patients with hypertension be worried about developing severe coronavirus disease 2019 ( COVID-19 )?

A comparison of the epidemiology of coronavirus disease ( COVID-19 ) outbreaks occurring in the first and second pandemic waves in care homes in Northern Ireland

Epidemiology of Blood Pressure and Predictors of Hypertension

Age-specific relevance of usual blood pressure to vascular mortality : a meta-analysis of individual data for one million adults in 61 prospective studies. The Lancet

Seroprevalence of anti-SARS-CoV-2 antibodies in Africa: A systematic review and meta-analysis

Malawi Governemnt Covid Database

The first and second waves of the COVID-19 pandemic in Africa : a cross-sectional study

Hypertension and related diseases in the era of COVID-19 : a report from the Japanese Society of Hypertension Task Force on COVID-19

Degree of matching and gain in power and efficiency in casecontrol studies

Hypertension and COVID-19 : Ongoing Controversies

Assessing the Impact of COVID-19 on TB and HIV Programme Services in Selected Health Facilities in Lilongwe

UNICEF Malawi COVID-19 Situation Report

First and second waves of coronavirus disease-19 : A comparative study in hospitalized patients in Reus

Risk Factors for COVID-19 in Patients with Hypertension

Worldometers Information for Coronavirus in Malawi

Prevalence of comorbidity in Chinese patients with COVID-19 : systematic review and meta-analysis of risk factors

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan , China : a retrospective cohort study

The authors declare no conflicts of interest.

Science and Technology (NCST)

Study conception: MROC, BWN, CM, PK, and BCM; study design: MROC, BWN, CM, PK and BCM; data collection: MROC, BWN, CM, PK and BCM; data analysis: MROC, BWN, CM, PK, SEM and BCM; manuscript preparation: MROC, BWN, CM, PK, SEM and BCM.All the authors contributed adequately towards the completion of this study. Their career background played important roles. All authors read and approved the manuscript.

Our sincere thanks go to the research funding support from Malawi Ministry of Health, Research Department through National Commission for Science and Technology (NCST). Furthermore, the staff of all the 28 districts in Malawi and all the institutions involved for the technical support throughout research implementation process. Lastly, we thank all the six research assistants who committed themselves to collect data across the entire country.