Profiles and Characteristics of Patients with Mild to Moderate COVID-19 Disease Phenotypes in a Teaching Hospital in Kano, Northern Nigeria

Introduction

At the end of 2019, a new pneumonia-causing coronavirus was identified from Wuhan in China, and for the purpose of uniformity, the World Health Organization (WHO) named the disease Corona Virus Disease 2019 (COVID-19), also known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Accordingly, the WHO declared the COVID-19 to be a disease of public health emergency of global concern.¹ As of November 16, 2021, the WHO reported 253,163,330 confirmed cases of COVID-19 across the globe, with 5,098,174 fatal outcomes. Of these, 6,186,377 COVID-19 cases were reported from Africa.² Nigeria had reported 213,175 PCR-confirmed cases of the disease with 2,968 associated deaths as of November 16, 2021.³

The clinical phenotypes of COVID-19 vary from asymptomatic infection through mild to moderate disease with symptoms comprising a variable combination of fever, cough fatigue, body aches, sore throat, loss of taste and/or smell as well as a host of other symptoms.⁴ In the severe form of the disease, it may progress to an acute respiratory distress syndrome (ARDS), and/or multiple organ failure, which could lead to death.⁵ More precise details of the disease (phenotypes), especially with respect to some unique clinical characteristics, are still evolving across the globe. Indeed, diverse subtypes of the disease not only have unique epidemiological features but also dissimilar laboratory findings. In Nigeria, Erinoso et al., reported the clinical characteristics of hospitalized patients in a cohort of 632 patients in Lagos⁶ while Otuonye et al.⁷ described the clinical profiles of 154 COVID-19 patients from the same State. Additionally, Elimian et al. described the cumulative incidence and case fatality of COVID-19 in Nigeria using retrospective data.⁸

Nigeria has a number of international airports, with the busiest ones being Lagos, Abuja, and Kano international airports. These points of entry represent potential sources of new COVID-19 infections into the country. While a large proportion of visitors to Lagos came from the United States and United Kingdom, those arriving in Kano are largely from the Middle East and Asia. Consequently, it is plausible to have imported cases of SARS-CoV-2 virus having varying clinical presentation and virulence resulting in clinical phenotypes. While the Nigerian Center for Disease Control (NCDC) continuously provides data on the burden of COVID-19 for each state of the country, little is known about predictors and clinical trajectory of non-severe COVID-19 disease phenotypes outside South-Western Nigeria after an exhaustive literature search.

Therefore, this study analyzed clinical characteristics of non-severe COVID-19 disease phenotypes confirmed using real-time Reverse Transcriptase Polymerase Chain Reaction (RT- PCR) in Kano City, Kano State. Kano city is the largest commercial city in Northern Nigeria with a population of about four million people.⁹ We also explored potential risk factors associated with the duration of hospitalization in order to provide useful information on disease phenotypes. After an exhaustive literature search utilizing the appropriate keywords on search engines comprising PUBMED, Web of Science, and Google Scholar, we found this study to be the first from Northern Nigeria that describes COVID-19 clinical phenotypes.

Methods

Results

Demographics

The median age of the patients was 33.0 years (IQR: 19-48), with individuals 21-40 years of age having the highest frequency (36.9%) (Figure 1). Most of the patients were male (n = 133 or 71.51%), and the median hospital length of stay was 10 days (IQR 8-18).

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Figure 1:

Age distribution of the COVID-19 patients in Muhammad Buhari Isolation Center

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Symptomatology

Of the 187 patients (study sample size) reviewed, 140 (74.8%) were asymptomatic. There was wide variability in symptom clusters comprising of fever, cough, sneezing, sore throat, runny nose, and body aches occurring in 80% of symptomatic patients (Table 3). Hypertension was the only additional comorbidity and was recorded in 26.7% of the study population. We noted significant differences in the frequency of occurrence of fever, cough, sneezing, sore throat, runny nose, and body aches between those discharged in less than ten days versus those discharged beyond ten days of hospitalization.

Table 3: Comparison of clinical attributes between those with “early” and “late” SARS-CoV-2 viral clearance in patients with COVID-19 in Kano, Nigeria

Symptoms	Early viral clearance (Time to discharge from isolation center (<10 days) N=98 (52.4%)	Late viral clearance (Time to discharge from isolation center (≥10 days) n=89 (47.6%)	P-value
Fever (30)^	23 (23.5%)	7 (7.9%)	0.05
Cough (26)^	12 (12.2%)	14 (15.7%)	0.15
Sneezing (9)^	0 (0%)	9 (10.1%)	0.02
Difficulty in breathing (10)^	3 (3.1%)	7 (7.9%)	0.12
Sore throat (14)^	5 (5.1%)	9 (10.1%)	0.04
Runny nose (8)^	3 (3.1%)	5 (5.6%)	0.04
Body ache (10)^	6 (6.2%)	4 (4.5%)	0.08
Fatigue (8)^	4 (4.1%)	4 (4.5%)	0.03
Anosmia (11)^	5 (5.1%)	6 (6.7%)	0.09
Agousia (1)^	0 (0%)	1 (1.1%)	0.09
Vomiting (4)^	4 (4.1%)	0 (0%)	0.114
Diarrhea (8)^	8 (8.2%)	0 (0%)	0.05
Chest pain (6)^	2 (2.0%)	4 (4.5%)	0.05
Loss of appetite (5)^	2 (2.0%)	3 (3.4%)	0147
Presence of any co morbidity (37)^	21 (21.4)	16 (17.9%)	0.62

SARS-CoV-2 viral clearance was confirmed using real-time PCR; ^: Number of patients with itemized symptom or feature

Using Kaplan Meier estimation, we found no significant differences in time to discharge from the isolation center between younger (< 50 years) versus older patients (≥ 50 years) [10 days vs. 11 days respectively; p = 0.32] (Figure 2). We also did not observe a significant difference between those with comorbidity versus those without comorbidity (p = 0.26), (Figure 3) as well as between symptomatic versus asymptomatic patients (p = 0.43) (Figure 4). However, we noted a faster viral clearance rate in patients on lopinavir versus those on chloroquine [p = 0.048] (Figure 5). Using Cox Proportional Hazard model, we did not find age (HR: 0.99, 95% C.I:0.98 -1.01), sex (HR:0.95, 95% C.I:0.31-2.94) and source of infection (HR:1.54, 95% C.I: 0.86-2.73) to be predictors of time to discharge among the study cohort with COVID 19.

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Figure 2:

Kaplan Meier estimation of time to discharge between those with age below and above age 50 years (with two-sided Log-rank test) Log-rank test p-value = 0.0818

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Figure 3:

Kaplan Meier estimation of time to discharge between those with versus those without co-morbidity (with two-sided Log-rank test) Log-rank test p-value = 0.7814

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Figure 4:

Kaplan Meier estimation of time to discharge between those with and without symptoms (with two-sided Log-rank test) Log-rank test p-value = 0.1638

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Figure 5:

Kaplan Meier estimation of time to discharge between those on Lopinavir versus those on chloroquine Log-rank test p-value = 0.048

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Almajiri (itinerary students)

There were 81 Almajiri scholars among our patients (mean age = 14.8 years SD = 3.5 years). They were all males and asymptomatic, most of them had “late viral clearance” 46 (57.1%). There was no significant difference in duration of hospitalization at the isolation center between Almajiris versus Non- almajiris. (Log-rank p = 0.416) (Figure 6).

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Figure 6:

Cumulative probabilities for time-to-discharge for COVID-19 positive Almajiris versus non-Almajiris displayed using Kaplan-Meier curves Log-rank test p-value = 0.416

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Discussion and Implications for Translation

Whereas coronavirus has been known to cause respiratory infection, SARS-CoV-2 appears to be a novel virus that displays unique interactions with the immune system, which had hitherto been naïve to it. Consequently, profiling its clinical characteristics is vital to enhance early detection and curtail disease spread. To characterize the clinical phenotypes of COVID-19 patients in Kano, Northern Nigeria, this study retrospectively evaluated the clinical presentation among a cohort of non-severe hospitalized patients in Kano, Nigeria. We found the patients to be mostly young and largely presenting with fever, cough, difficulty in breathing, and sore throat, with most of them hospitalized for a little over a week. Earlier studies in Nigeria had similarly found young patients to be the most commonly affected.^13,14The finding is similar to reports from Saudi Arabia among patients with non-severe disease.^15,16 This is in contrast to the higher age reported among patients with mild-to-moderate clinical features in China.^5,17The reason for the discrepancy might be largely related to the variance in admission criteria in the China study compared to ours, as well as differences in the age admixture of our cohort. Perhaps it might also reflect a wider gap in demographic age spread between these populations. It is not surprising to find a larger proportion of young persons in our cohort since our hospital a priori admitted persons with non-severe disease. On the contrary, severe disease is commoner among older patients.¹⁸

Vulnerabilities to contagions are especially related to the level and duration of exposure.¹⁹ The longer a person is exposed to a source of infection, the higher the likelihood of being infected. Traditional gender roles attributed to different gender strata in Africa demand men to work outdoors and secure resources for the family while women stay at home. Thus, men are more likely to be outdoors and run the risk of breaching social distancing requirements leading to a higher risk of SARS-CoV-2 infections among males.

The policy of our COVID-19 isolation center at the time of the study was to maintain in-patient care until a patient had negative RT-PCR viral test results. Therefore, the duration of hospitalization in our study of 10 (IQR 8-18) days represents a surrogate marker of time to RNA viral conversion. A study in Tunisia reported the median period to viral clearance to be 20 (IQR 17-32) days.²⁰ Conversely, a study in Qingdao, China, reported 14 (IQR: 10-18) days as the median duration to viral conversion.²⁰The differences across studies might be linked to the spectrum of disease severity typically observed in COVID-19 patients.

At our center, patient assignment to receive either chloroquine or Lopinavir was at the discretion of the physician on duty at the time of admission. We could, therefore, not objectively assess the results of the treatment impact observed in the study. Further, our results did not reveal any significant association between age, presence of comorbidity, and occurrence of symptoms with time to RNA conversion as outcome. It is important to contextualize the reasons behind our choices of drugs. There was no established evidence-based efficacious treatment for COVID 19 as at the time of care of the index cohort in 2020. All therapies then were exploratory but scientifically based on in-vitro drug performance, preclinical studies, and observational trends. Consequently, our choice of medications was anchored on prevailing anecdotal evidence similar to the practice in other countries.^21-23Similar to several other studies, we found contact with an infected person to be the commonest means of SARS-CoV-2 spread.^5,24-26 Respiratory infections are often transmitted by the propulsion of droplets of varying sizes. Social habits and the basic requirement of human interactions render human-to-human contact an inevitable mechanism for transmission. These dynamics have far-reaching implications for COVID-19 control measures, considering the need to enforce social distancing to mitigate further spread.

The itinerate Quranic school students, known locally as Almajiri children, are a vulnerable population. They are mostly displaced having left their place of birth, traveling far in search of knowledge, Kano had over 3,000 Almajiri schools, with approximately one million students.²⁷ These students faced one of the highest medical and social challenges during the COVID-19 pandemic having no strong social support system. Furthermore, they were repatriated to their places of birth in spite of the difficulty in movement imposed by the then prevailing “lock-down.”²⁸ Indeed, by virtue of the overcrowding in Almajiri schools and sustained displacement, the pupils were at a heightened risk of infection with SARS-CoV-2. Moreover, they serve as a veritable source of infection to the larger population.²⁸

The aim of the study was to delineate COVID-19 phenotypes in Northern Nigeria based on a syndromic approach. Although the signs and symptom clusters observed in our patients are not specific to COVID-19, however, in the setting of an ongoing epidemic, they do offer an opportunity for guided clinical screening based on symptom clusters to enhance case detection efficiency.

Our study exhibits a number of limitations. First, only persons with non-severe SARS-CoV-2 infection were admitted to the MBSH isolation center, which limited the study sample size and ultimately power required to make firm conclusions. In addition, comparison with severe cases of COVID-19 disease phenotype was not feasible given the facility setting. Second, evaluation of co-morbidity status was mostly based on self-report, and hence, we could have missed some important comorbidities not volunteered by patients. Nonetheless, to the best of our knowledge, this study represents the largest that has described COVID-19 clinical phenotypes from Northern Nigeria.

In conclusion, the findings of this study have a bearing on the surveillance and diagnosis of COVID-19 in Nigeria. While the plethora of clinical features may not be limited to SARS-CoV-2 viral infection, the healthcare team should consider these symptom clusters in addition to cognate contact and travel history when confronted with a suspected case of COVID-19 infection.