Discussion
In this prospective study, we describe the characteristics and outcomes of 56 treated patients with COVID-19 at two hospitals in Uganda. The median age of these patients was 33 years, and 67.9% of the patients were male. The predominance of male gender among patients with COVID-19 is similar to what has been reported elsewhere.7 17 Like most respiratory diseases COVID-19 predominance in men may reflect exposure dynamics since men are usually more outdoor and more likely to be exposed than women. The mean age we observed is, however, different from reports in China, Europe and the USA.17 In China, Guan et al7 reported a mean age of 47 years, while in the USA, Richardson et al18 reported a mean age of 63 years. The young age of the Ugandan patients with COVID-19 is probably a reflection of the general population structure where our population is composed mainly of young people.19 Another reason could be the source of the initial patients with COVID-19 in Uganda, which was mainly composed of youthful travellers returning from their workplaces abroad. We also note that the 56 patients include eight children belonging to a choir who were returning from abroad. This could also have skewed the cohort’s age downwards.
We found that up to 56.1% of the patients were asymptomatic and not in keeping with most studies on hospitalised patients. In most studies, over 80% of the patients have one or more COVID-19 symptoms by the time of hospitalisation.4 7 17 Our results are, however, in line with findings from a study by Arons et al20 and Sutton et al.5 In the study by Arons et al20 among 89 residents of a skilled nursing home, 56% of persons found positive were asymptomatic.20 The testing in this study was part of a survey. In the case of Uganda, most of the persons were tested as part of routine surveillance because they either had travelled or had been in contact with a confirmed case. It seems therefore that the absence of symptoms could be due to early detection. In the study by Arons et al20 referred to earlier, they reassessed the asymptomatic persons again. They found that 24 of the 27 asymptomatic patients subsequently developed symptoms (median time to onset of 4 days). This was not the case among our patients, suggesting that there could be other reasons for lack of symptoms in our cohort.20 Asymptomatic disease has gained attention following the finding that disease transmission occurs even in the absence of symptoms.21 If indeed most patients with COVID-19 in Uganda and Africa will be asymptomatic, control efforts need to be geared towards mass testing as many of those infected will not be sick and will therefore not be presenting at health facilities for testing and treatment.
Comorbidity has been a common finding in patients with COVID-19 and has been found to be associated with worse outcomes.4 7 17 22 In this study, we found that up to 26.8% of the patients reported at least one comorbidity (any of tuberculosis, HIV, hypertension, diabetes, asthma, COPD, cancer, chronic kidney disease, chronic liver disease or chronic neurological disorders). The most common comorbidities were hypertension (10.7%), diabetes (10.7%), cardiovascular disease other than hypertension (8.9%) and HIV (7.1%). The rate of having any of the listed comorbidities and the individual comorbidity rates are much lower than reported elsewhere.7 17 The lower rates are probably a reflection of lower rates of the same diseases in the general population but could also be due to lower rates of diagnosis of these diseases in the general population. A case in point is hypertension; only six patients reported a history of hypertension. However, as can be seen in table 1, 37% of the patients had BP>130/90 mm Hg, and 27.8% had BP higher than 140/90 mm Hg. Living with undiagnosed hypertension has been reported in several studies in Uganda.23 A study by Kayima et al23 found that among 553 hypertensive persons, only 13.7% were aware of their diagnosis. The underdiagnosis notwithstanding, 37% prevalence of hypertension in these patients is higher than that found in general population studies in Uganda.23–25 Anxiety due to the fear of the disease could explain this high baseline BP. Further research is needed to establish if there is a direct link between SARS-CoV-2 virus infection and high BP, especially through the hypothalamic–pituitary–adrenal axis.
The rates of laboratory derangements investigated were lower than those reported in cohorts elsewhere, in keeping with the mild nature of the disease in the patients we studied.7 For example, we found leucopenia in 10.6% of the patients, but Guan et al7 found it at 33.7% among Chinese patients; lymphopenia was 11.1% compared with 80.4% found in China. The same applied to CXR abnormalities where we found that only 3 out of 21 patients who underwent this examination had abnormalities. In the Guan et al7 study, this rate was 59.1%.
In this initial cohort of 56 patients, no death, admission to ICU or mechanical ventilation was observed. With the exception of two patients, almost all had mild disease at admission and none deteriorated to severe or critical disease, a clinical trajectory that has not been observed in other countries. This patient, a 40-year-old man, was admitted with RT-PCR-confirmed COVID-19. He had been previously diagnosed with hypertension treated with calcium channel blockers and a thiazide diuretic. He had a week-long cough and during his stay, low SpO2 ranging between 92% and 95% was noted. His baseline CXR (2 April) showed bilateral infiltrates (figure 3A and follow-up CXRs (6 and 17 April, respectively; figure 3B,C). The 17 April CXR showed marked improvement. On 19 April before discharge, we performed chest CT scans on this patient. The scan showed multiple peripheral and subpleural GGOs with associated interlobular septal thickening in all segments of the lung parenchyma. There was coalescing with a tendency to form air space consolidation. Selected slices from the chest CT scans are shown (figure 3). Although CXR had shown marked improvement, a CT scan performed later showed presence of pathology (figure 4).
Figure 3Posteroanterior chest X-ray images of a 40-year-old male hypertensive Ugandan admitted with reverse transcriptase PCR confirmed COVID-19 at baseline (A), 4 days (B) and 15 days (C) postadmission at Mulago National Specialised Hospital.
Figure 4CT scan images of the 40-year-old male Ugandan patient with COVID-19 at discharge (17 days postadmission).
Death, admission to ICU and mechanical ventilation were observed at rates of 21% death, 14.2% admission to ICU and 3.2% mechanical ventilation in a study involving 5700 Americans by Richardson et al.18 In China, the rates were 6.1% for death, 5% for admission to ICU and 2.3% for mechanical ventilation.7 The reasons for the lack of these adverse outcomes are not clear to us, but we think it could be due to the small sample size. It could also be due to the mild nature of the disease, with the reasons for the disease being mild not known at this point in time. The low rates of comorbid disease are probably a key factor since these have been consistently found to be associated with adverse outcomes.7 18 22 Several studies suggest that the viral load patients with COVID-19 exhibit is linked to the initial dose of the virus at the time of infection, and the viral load in turn determines the severity of the disease, although most of such studies are small and retrospective.26 27 Most of the Ugandan patients were detected among travellers whose exposures during travel could have been lower, hence low viral load at the beginning of infection and hence mild disease. Further research is needed if this similar trend continues to be observed.
Most of the patients in this cohort received supportive care and many received antibiotics. The main driving factor for the high antibiotic use is the entrenched practice of prescribing antibiotics for respiratory symptoms in our setting. In addition, there is evidence that secondary bacterial infection occurs following respiratory viral infection. When they occur, they are usually due to Streptococcus pneumonia, Haemophilus influenza, and Staphylococcus aureus.28 However, secondary bacterial infection in COVID-19 has been reported to be rare.18 In view of this finding that secondary bacterial infections are uncommon in COVID-19 as opposed to other viral pneumonias, we do not recommend routine use of antibiotics in the treatment of COVID-19. A comparison of 29 patients who received HCQ to 24 patients who did not received HCQ showed that there was no difference in terms of mortality, admission to ICU, mechanical ventilation and TTCR. TTCR was shorter for the HCQ group, but it did not reach statistical significance. HCQ is prescribed in many centres around the world for the treatment of COVID-19. HCQ was reported to result in improved viral clearance in a small study done in France.12 A recently rapid review has identified 38 studies on the use of HCQ for treatment of COVID-19 (8 randomised clinical trials and 30 observational studies).29 This review notes the low methodological quality of the identified studies but concludes that the available evidence is sufficient to conclude that HCQ has no benefit in the treatment and prevention of COVID-19.29 Our findings, although from a small observation study, are in line with studies included in this review.
Our study has limitations, including the small sample size, and limitation of tests, including absence of viral clearance monitoring. The outcomes by HCQ are also limited by lack of randomisation to HCQ treatment.
In conclusion, most of the patients with COVID-19 presented with mild disease and exhibited a clinical trajectory not similar to other countries. Outcomes did not differ by HCQ treatment status in line with other concluded studies on the use of HCQ in the treatment of COVID-19.
