Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan

Introduction

In December, China reported a group of pneumonia cases of unknown etiology that were later identified to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)^1,2. On March 11^th, 2020, the World Health Organization (WHO) categorized coronavirus disease 2019 (COVID-19) as a global pandemic³. Patients with COVID-19 frequently present with a cluster of different respiratory symptoms, including fever, chills cough, shortness of breath, sore throat, and new loss of taste and/or smell within 2 to 14 days after exposure in most cases⁴.

Coronaviruses belong to viral family Coronaviridae (order Nidovirales) and include viruses approximately 26–32 kilobases in size with a positive-sense single-stranded RNA genome (+ssRNA)⁵. The Coronaviridae family contains four genera, one of which is the Betacoronavirus genus, which SARS-CoV-2 belongs to 6.

Initial assessments of the epidemiologic characteristics and transmission dynamics showed that the basic reproductive number (R₀), which is defined as the expected number of additional cases that can directly be generated by one case in a population susceptible to infection on average over the course of its infectious, range from 2.2 to 3.58^7,8, with the potential for asymptomatic transmission being a major concern for most of previous investigations.

The first identified case of COVID-19 in Jordan was on March 2^nd, 2020, a returning traveler two weeks prior to quarantine procedures⁹. On March 13^th, a wedding ceremony led to a large outbreak of COVID-19 cases in northern Jordan¹⁰, after which a strict lockdown took place and five tertiary hospitals were selected to provide medical care for patients suspected or diagnosed COVID-19 cases^9,10.

Healthcare systems in low- and middle-income countries may face serious limitations in capacity and accessibility during a pandemic, leading to worse clinical outcomes and an increase in mortality rate¹¹. Therefore, the aim of this study is to investigate the predictors of increased length of hospitalization among COVID-19 patients, in order to provide evidence-based public health outbreak response strategies for COVID-19 and future pandemics.

Methods

Results and discussion

Discussion

In spite of the great progress in understanding COVID-19, a therapeutic or preventive solution is yet to be achieved¹⁴. Consequently, better management of medical facilities during the next phase of this pandemic is crucial in improving the outcomes in these patients¹⁵. In the present study, smoker, as well as patients presenting with malaise and elevated WBCs at presentation had shorter hospital stay, while loss of taste and chills or rigors at presentation were associated with lengthier in-hospital stay.

Several previous studies investigated the clinical manifestations of COVID-19. Most common presenting symptoms in most of these studies were fever, cough, dyspnea, malaise and myalgia^16,17. Interestingly, it has been suggested that anosmia (loss of smelling sense) and ageusia (loss of taste function) can represent the first or only symptomatology¹⁸, while an investigation from Italy found that 64% mildly symptomatic patients had impaired olfaction¹⁹.

Remarkably, even though multivariable linear regression analyses in the current study did not show significant correlation between demographic factors and the length of in-hospital stay except for smoking habit, an investigation from Germany revealed that those with preexisting respiratory diseases, obese patients, and those with persistently elevated inflammatory markers are at increased risk of developing acute respiratory distress syndrome (ARDS), which will prolong their hospitalization period²⁰. Moreover, a study conducted in China found that severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of c-reactive protein, d-dimer, lactate dehydrogenase, alanine aminotransferase, ferritin, IL-2R, IL-6, IL-10, and TNF-α²¹. In the current study, patients with elevated WBCs count had shorter in-hospital stay. Immunocompetent WBCs play a significant role in systemic inflammatory response to infection, with neutrophil-lymphocyte count ratio being significantly higher in mortality cases of community-acquired pneumonia²².

An interesting finding in our study is that smokers had shorter in-hospital stay, moreover, only 22% of hospitalized COVID-19 patients were smokers. There is a controversy in the current literature about the role of smoking and nicotine in COVID-19^23,24. It is postulated that smokers are at higher risk to get respiratory tract infections and develop more severe illness, due to the preexisting bronchopulmonary damage, reduced muco-ciliary clearance, and the local inflammatory status²³. Some reports, however, showed lower COVID-19 related mortality and morbidity in smokers²⁴. Nicotine, as a cholinergic agonist, inhibits pro-inflammatory cytokines such as TNF, IL-1, IL-6 by binding acetylcholine receptors (nAChR). These cytokines, among the others, might result in the notorious feature of this illness, the cytokine storm. Therefore, it was hypothesized that COVID-19 is a disease of nicotinic cholinergic system. Another supporting observation is that patients with ageusia in our sample had longer in-hospital stay; this sensory disturbance is mainly related to the cholinergic system of the brain, and it might indicate that such patients are having more extensive disease, or technically, nicotinic cholinergic dysfunction^23,24. Although it is not wise or acceptable to advice people to smoke, this might shed the light on the promising role of nicotine in preventing and treating COVID-19 infection.

The rapid upsurge in the number of confirmed cases makes the control of the spread of COVID-19 and its treatment challenging²⁵. Several ongoing clinical trials will soon confirm or disprove the usefulness of several candidate medications in treating COVID-19²⁶. Studies investigating the use of hydroxychloroquine were unable to confirm its benefit on in-hospital outcomes of COVID-19 patients²⁷. On the other hand, dexamethasone has shown a decrease in the 28-day mortality among those who were receiving respiratory support, with both of dexamethasone and methylprednisolone being equally effective in treating moderate to severe COVID-19 cases^28,29. With no definitive method of prevention or treatment being available to date, precautions should be made in order to control the spread of COVID-19, including proper hand hygiene, isolation of infected or suspected persons in properly ventilated hospitals, social distancing, discouraging large gatherings, and avoiding direct contact with suspected animal reservoir hosts³⁰.

The main limitation of this study is that it did not investigate the predictors of in-hospital mortality of COVID-19 patients. Previous studies suggested that older age, high Sequential Organ Failure Assessment (SOFA) score, and elevated d-dimer are associated with poor prognosis^31,32. However, upon plotting mortality against the incidence of COVID-19, a significant positive correlation was found, suggesting that mortality is associated with heavier healthcare burden³³. Hence, understanding the predictors of prolonged hospital stay and prognostic factors are crucial in decreasing the mortality of any pandemic. Moreover, we recommend future studies to take into consideration duration and severity of each symptom in order to develop a better understanding of the clinical course of COVID-19. The main strength of our study is that, in Jordan, all COVID-19 patients were hospitalized during the study’s timeframe, regardless of the severity of their illness. Therefore, our sample gives a good opportunity to observe the natural progression of COVID-19 under controlled conditions.

Conclusion

Our study found that the most common presenting symptoms of COVID-19 are cough, malaise, and headache. Smoking, presenting with malaise or elevated WBCs were associated with shorter hospital stay, while loss of taste and chills or rigors at presentation were associated with a longer in-hospital stay. Such findings are important in risk stratifying COVID-19 patients according to their presenting symptoms and past medical history. Although it is not wise or acceptable to consider smoking behaviors, future research should shed light on the role of nicotinic receptors in mitigating this illness.

Data availability