Predictors and outcomes of COVID-19 patients with hypoxemia in Lagos, Nigeria

INTRODUCTION

The coronavirus disease 2019 (COVID-19) pandemic is the current public health concern ravaging the whole world since the first cases were discovered in Wuhan, China in December 2019.^[1] This infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), affects people of all ages in various degrees, ranging from asymptomatic or mild disease in majority (81%) of cases, to severe (14%), and critical illness (5%) requiring intensive care and ventilation.^[1]

Data on clinical presentation, course of illness and prognosis, are largely from studies done in China, Europe, and the United States of America (USA).^[1-5] As COVID-19 cases are gradually increasing in parts of South America and Africa including Nigeria, it is important to examine the risk factors or predictors of severe disease and mortality in our setting to increase preparedness and management, considering the devastating impact it has had on the health system in high income countries.^[6-8] This understanding will enable risk stratification and help to identify those who may likely need close monitoring and care. It would also allow channeling scarce resources and manpower toward those who would need them the most to potentially reduce morbidity and mortality.

Hypoxemia has been identified as an independent risk factor for mortality in COVID-19 patients regardless of age or sex.^[3,9-11] A study in Israel reported that nasopharyngeal viral load predicted hypoxemia and that age and blood oxygen saturation were independently associated with mechanical ventilation and death.^[12] Asymptomatic hypoxemia, which refers to a scenario where an individual has a reduced oxygen saturation (SPO2) indicating hypoxemia without having associated clinical features such as dyspnea or signs of respiratory distress, has also been associated with poor prognosis in COVID-19 patients.^[13] Other risk factors for increased severity and mortality identified in other studies include older age, sex, dyspnea, and presence of comorbidities such as hypertension and diabetes mellitus (DM).^[2,3,14,15] The role of these risk factors in the Nigerian setting has not been extensively reported.

This study, therefore, aimed to assess the profile of COVID-19 patients with hypoxemia in Lagos, Nigeria and identify their associated socio-demographic and clinical risk factors, predictors, and outcomes. This could provide the much-needed data, to inform COVID-19 case management and policy in Nigeria.

MATERIALS AND METHODS

RESULTS

Baseline characteristics of study population

A total of 557 patients were managed between April 7 and October 7, 2020. Only 266 had SPO2 readings recorded and were analyzed. [Table 1] shows the baseline characteristics of the study population. The age of study population ranged between 7 and 86 years, mean ± SD of 49.80 ± 16.68 years. There were more males; 183 (68.8%) with a M: F ratio of 2.2:1. Most of the cases 99 (37.2%) were in the middle-aged age group (40–59 years) and 85 (32.2%) in the old age group (≥60 years).

Table 1: Baseline characteristics of study population.

Variable	Frequency	(%) n=266
Age group (years)
0–17	2	0.8
18–39	78	29.3
40–59	99	37.2
≥60	85	31.9
Not specified*	2	0.8
Sex
Male	183	68.8
Female	83	31.2
Symptoms
Present	185	69.5
Absent	81	30.5
Comorbidity
Present	127	47.7
Absent	139	52.3
Disease category
Asymptomatic	81	30.5
Mild	58	21.8
Moderate	43	16.2
Severe	79	29.7
Critical	5	1.9

*Exact age not recorded, stated as adult in medical records

About 185 (69.5%) of the cases had symptomatic disease; comorbidities were present in 127 (47.7%) of the study population. Disease category/severity was asymptomatic in 81 (30.5%) and severe in 79 (29.7 %) of the study population. SPO2 measurements ranged from 33% to 99%, Mean ± SD of 88 ±12%.

[Figures 1 and 2] show the spectrum of symptoms and comorbidities of the cases, respectively. The common symptoms were difficulty breathing in 95 (34.7), fever in 91 (34.2%) and cough in 77 (28.9%) of the cases; while the common comorbidities were: Hypertension; 86 (32.3%) and DM; 47 (17.7%).

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Figure 1:

Spectrum of symptoms of cases.

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Figure 2:

Spectrum of associated comorbidities.

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DISCUSSION

This study found hypoxemia determined by pulse oximeter measurements to affect about one-third of the COVID-19 cases. Seventy-six (28.6%) already had hypoxemia at the time of admission into hospital. The significant predictors of hypoxemia were fever, difficulty breathing, and old age ≥60 years. Although most of the hypoxemia cases were discharged, there was a high CFR of 31.4% among them. Hypoxemic cases had a significantly shorter length of hospital stay and odds of dying were 14 times higher compared to those without hypoxemia.

Similar findings of 28.9–41% of patients being hypoxemic on admission have been reported in studies in Nigeria and the US.^[10,18] Patients with hypoxemia were likely to be older, male and had hypertension compared to those with SPO2 > 90% in our study which was consistent with the report from Wuhan, China.^[11] However, association between hypoxemia and sex was not significant in the current study (P = 0.96) which was also corroborated by the Wuhan study. Studies from Nigeria and other countries agree with the finding of association between older age and severe COVID or hypoxemia.^[5,19]

Fever, dyspnea, cough, and DM were also found to be significantly associated with hypoxemia in this study. Fever, dyspnea, and cough are clinical features of inflammation and pneumonia which causes hypoxemia in COVID-19 patients, as less of the lung parenchyma becomes available for gaseous exchange.^[20]

The relationship between hypoxemia and comorbidities differs among the various comorbidities, but the common denominator is the level of inflammation, with the result being acute respiratory distress syndrome. Some of the reasons may include increase in the expression of Angiotensin-converting enzyme 2 (ACE2) receptors, especially on the heart and blood vessels, leading to increased viral binding, and tissue pathology in hypertension.^[21,22] Furthermore, hypertensive patients may be on ACE inhibitors, which have been linked with increase in the amount of ACE2 receptors that are expressed on the various end organs.^[23] Furthermore, certain chronic conditions (e.g., DM and obesity) are associated with underlying inflammation, associated with endothelial dysfunction, and increased baseline inflammatory markers, predisposing them to a heightened inflammatory response to COVID-19 infection.^[24] These findings are consistent with findings by Jang et al.^[9] that reported association of fever and DM with hypoxemia. Ayinbuomwan et al.^[25] also reported significant association of hypoxemia with dyspnea and presence of underlying disease. Conversely, only dyspnea was significantly associated with hypoxemia in a study in China.^[11]

Other symptoms and comorbidities were not associated with hypoxemia in this study, which is contrary to other studies that have found some co-morbidities such as obesity^[18,21,26] and cancer^[27,28] to be associated with severe disease and hypoxemia. The disparity may be due to the small number of cases with these comorbidities in the current study. Cases with hypoxemia were also more likely to have symptoms and at least one comorbidity, compared with those without hypoxemia, which agrees with report by Xie et al.^[11]

The independent predictors of hypoxemia in this study were fever, old age ≥ 60 and difficulty breathing. Other risk factors such as hypertension, diabetes, and cough though associated with hypoxemia were not significant predictors. It is, therefore, important to advocate for early presentation to hospital for those 60 years and above and those with dyspnea, as well as those with these symptoms and comorbidities, for they may be at increased risk of having hypoxemia necessitating the need for oxygen therapy. Early detection of hypoxemia and institution of oxygen therapy or ventilatory support could improve the prognosis of these cases.

In terms of outcomes, there was high overall mortality, or CFR of 13.9% in this study. This may be due to COVID-19 being a novel disease with paucity of effective therapies, especially earlier in the pandemic when there was poor knowledge of the disease. Other studies done in Nigeria, China, and the US have found a range of between 2.6–33%.^[5,11,14-19] These variations may exist due to the differences in cohorts of patients studied. Our study had a mix of asymptomatic and symptomatic patients with varied severity of illness, while some other studies like that of Buckner et al.^[18] in the U.S. with a high CFR of 33%, had a population of patients who were older and had a high prevalence of comorbidities and severe disease. Furthermore, CFR was higher among hypoxemic patients (31.4%) compared to non-hypoxemic patients (3%) in this study. They were also 14 times more likely to die than those without hypoxemia. The relationship between hypoxemia and mortality may reflect the lack of COVID-19 ICU facilities during the 1^st wave of the pandemic. There were very few ICUs in Lagos at that time, which were also expensive and not within the reach of many. Furthermore, hypoxemia contributes to the inflammatory process, thereby worsening the ventilation/perfusion V/Q mismatch, leading to worse outcomes.^[29] Similar finding of higher mortality rate in hypoxemic versus nonhypoxemic cases of 68.6% versus 1.1% (Hazard ratio of 47) was obtained in study by Xie et al. in China.^[11] They also reported that oxygen saturation (SPO2) >90.5% predicted survival with a sensitivity of 84.6% and specificity of 97.2%, and that dyspnea was independently associated with mortality.

A U.S. study^[5] also reported 2 times greater odds of dying in hypoxemic patients. Similarly, a single center study in Northern Nigeria,^[10] found that those with hypoxemia were 2.5 times more likely to die, though they had a small sample size of 45 cases, while a study in Lagos found dyspnea to be associated with increased mortality in COVID-19 patients but did not report oxygen saturation values.^[14] Most of the deaths (54.1%) occurred within 48 hrs; 97% within 10 days, like median of 3 days (IQR 1–7) in a study by Elimian et al.^[15] in Nigeria. Early mortality may be due to unavailability of facilities for ventilatory support or late presentation which has been reported in other studies from Nigeria.^[14]

Timing of hypoxemia was also important, as those with hypoxemia on admission in hospital were 3 times more likely to die than those who developed it later during hospitalization. Similar finding was reported in a study in Korea among elderly COVID-19 patients in whom hypoxia on admission was associated with poor outcome and was a risk factor for ventilation and death.^[30] Hypoxemia on admission would indicate a severe presentation which is often related to a poor outcome.

One out of every 3 COVID-19 cases in our cohort had hypoxemia. The implication of this is the increased need for oxygen therapy and possibly ventilation if this is not effective. Access to oxygen is limited in a resource poor country like ours^[31] and COVID-19 increased the demand for an already scarce commodity. The impact of hypoxemia on mortality is huge as most studies including the current one have shown that it is one of the main predictors of mortality.

Objective measurement of oxygen saturation using the pulse oximeter is the easiest way to detect hypoxemia since it is easy to operate and portable. However, in our resource limited country, this seemingly inexpensive equipment may not be available to health facilities, let alone individuals. Therefore, early diagnosis of COVID-19 and presentation in hospital of at-risk individuals before severe hypoxemia develops cannot be over-emphasized.

CONCLUSION

Hypoxemia occurred in one out of every three patients with COVID-19 and they were 14 times more likely to die than those without hypoxemia. Fever, old age ≥ 60 years, and dyspnea were independent predictors of hypoxemia. Early presentation to hospital and SPO2 monitoring of COVID-19 cases with these features is essential for early identification of hypoxemia. Detecting and treating hypoxemia early could lead to a better prognosis.