Clinical course and disease outcomes in hospitalized patients with 2019 novel corona virus disease at Ibn- Al Khateeb Hospital in Baghdad, Iraq

Background: the novel coronavirus (2019-ncov), formally known as severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the etiological cause of the (corona virus disease 2019) covid-19, appeared in wuhan, hubei province, china. On 11 march 2020, the world health organization (who) declared this disease as a pandemic. As new information on the clinical characteristics, treatment options, and outcomes for covid-19 emerges approximately every hour, physicians should keep themselves up-to-date on this topic. Objective: to study the demographic features, clinical signs and symptoms and certain vital and laboratory findings of covid-19 hospitalized cases; and to identify the used medication, complications, length of stay at the hospital and disease outcomes of confirmed covid-19 cases. Patients and methods: a descriptive cross-sectional study with analytic elements was conducted at ibnal khateeb hospital, baghdad on covid-19 patients admitted to the hospital from 1st of march to 4th of may 2020. All inpatients of all age groups, diagnosed as covid-19 and had a definite outcome (recovered and discharge or death) during the period of the study were included. Results: the mean age ± sd for the patients included in the study was = 37.9±18.85 years, with 51.2% being males. The outcome was statistically significantly associated with age, marital status, hypertension, disease severity at admission and length of stay at hospital. Conclusion: this study found that age was associated with disease outcome. Care, attention and monitoring should be taken into consideration for hypertensive patients. Patients’ initial signs and symptoms of dyspnea, weakness and sore throat were significantly associated with disease outcome.


Introduction:
Novel coronavirus (2019-nCoV), officially recognized as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological mediator of the ( 3 The difficulties in detecting asymptomatic carriers, who often do not know they are infected, undoubtedly facilitates the spread and appearance of unexpected disease foci whose traceability becomes impossible in several cases. 5 Corona-viruses are enveloped, non-segmented positive sense RNA viruses whose name is due to projections of club-shaped spikes. 6,7 The clinical presentations of the illness vary, but over the course of the disease, most persons with COVID-19 will experience symptoms (fever, dry cough, fatigue, rhinorrhea, myalgia, sore throat, new loss of taste or smell, headache and less frequently diarrhea). The infection will progress, affecting the lower respiratory tract that causes dyspnea, increased respiratory rate, decreased oxygen saturation and finally respiratory failure, septic shock and multi-organ dysfunction.8,9 COVID-19 presents itself after a median incubation time of around 5 days (95% CI, 4.5 to 5.8 days), with a range of 0-24 days and the vast majority (97.5%) of patients being symptomatic within 11.5 days (CI, 8 investigations (temperature, pulse rare, oxygen saturation), comorbidity (diabetes mellitus, heart disease, hypertension, chronic lung disease, cancer, chronic renal failure and arthritis), case severity classification (mild, moderate, severe or critical)21, treatment (hydroxychloroquine, Tamiflu, kaletra, azithromycin, antibiotics, bronchodilators, antipyretics, corticosteroids, immunomodulators, convalescent plasma, mechanical ventilator, oxygen and others), complications (lung fibrosis, heart failure, renal failure and others) and outcome data were collected. Outcome: All patients who received treatment completed a planned therapy, the majority received hydroxychloroquine 400mg for the first day then 200 mg twice daily for 5 days, azithromycin 500mg for the first day then 250mg once daily for 5 days, oseltamivir 150 mg for the first day then 75 mg twice daily for 5 days, antipyretic if axillary body temperature ≥37.5oC, other treatment options were added according to physician judgment. The outcome of COVID-19 patients was either recovered / discharged or death. To declare that the patient is recovered, real technique-polymerase chain reaction (RT-PCR) tests results were collected at the end of the treatment, nasopharyngeal and throat specimens were obtained from patients by using specific kits by a qualified health-staff and sent to the Central Public Health Laboratory in Baghdad for RT-PCR testing. The patient was not discharged unless two PCR-tests were negative at least 24 hours apart. According to the WHO interim guidance, 28 January and 13 March 2020, clinical management of severe acute respiratory infection when novel corona virus (nCOV -2019) infection is suspected, repeat samples of URTs should be obtained in hospitalized patients with confirmed 2019-nCoV infection to demonstrate viral clearance. The frequency of specimen selection may depend on local circumstances but should be done at least every 2 -4 days until there are two negative consecutive results (URT sample) at least 24 hours apart in a clinically recovered patient 19, 20.

Statistical analysis:
The statistical analysis was performed using statistical package for social science (SPSS-23). Categorical data was formulated as numbers and percentages, normal distribution numerical data were described as means and standard deviations. The Chi-square and fisher's exact probability tests were used, where necessary. A P value of ≤ 0.05 was considered significance.

Results:
The sample size was 127 COVID-19 patients. Of them, 23 (18.1%) were at age group 30-39y with mean age ± SD= 37.9±18.85, male patients were 51.2%, while female patients were 48.4%. According to education level and jobs, we included 121 out of 127 because children <6 years old (the age for entering the school in Iraq) were excluded. There was a statistically significant association between age groups and COVID-19 patients' outcome, as 26.3% of those aged 60 and above died. There was no statistically significant association between gender, education level, job, history of smoking and COVID-19 patients' outcome. Out of 116 COVID-19 patients; 74.1% were married as illustrated in table 1. Out of COVID-19 patients 68.5% does not have any comorbidity, 4.6% of them died. There was a no statistically significant association between having comorbidities and COVID-19 patients' outcome except for hypertension. There was no statistical association between COVID-19 patient outcome and using chronic drugs. 6.3% of COVID-19 patients were severely ill patients, 3.9% were critically ill patients, all critical patients died 100%, whereas 74.8% were mild and 15.0% were moderate, none of them died 0.0%. There was a statistically significant association between patient severity status and COVID-19 patients' outcome as illustrated in table 2. Thirty-one (24.4%) of COVID-19 patients in the study had no signs and symptoms, but were contacts of a positive case. They were investigated and when their test result was positive, they were admitted to hospital. Although there was no statistically significant association between having signs and symptoms and COVID-19 patients' outcome, but there was a statistically significant association between those having sore throat, dyspnea, weakness and COVID-19 patients' outcome, as shown in table 3. After two days of starting treatment, all COVID-19 patients that had normal oxygen saturation recovered (100%), whereas all those with low oxygen saturation died (100%). After completing the treatment; all COVID-19 patients that had normal oxygen saturation recovered (100%), whereas all those with low oxygen saturation died (100%). Also, all COVID-19 patients that has high pulse rate died (100%), while all COVID-19 patients (100%) that had normal pulse rate recovered as demonstrated in table 4. Nine patients (7.1%) refused to receive treatment, but they were admitted because at the beginning of the outbreak, any case with COVID-19 whatever its severity (mild, moderate, severe, critical) must be admitted to the hospital for follow up since the numbers of the cases were small then and such measures were possible. Although there has been no statistically significant association between receiving treatment (in general) and outcome, but there was a significant association between those who received kaletra, antibiotics, corticosteroids, anticoagulants,        Discussion: COVID-19 is one of the important public health issues that have implications for a significant number of morbidity and mortality. A sample of 127 positive COVID-19 hospitalized cases has been included in our study (117 recovered and discharged and 10 died), case fatality rate in our study=7.87%. As in the Al-Rusafa Health Directorate, we lack epidemiological research on the outcome of COVID-19 and the factors associated with it, our analysis identified in detail the major differences in demographic, clinical characteristics, diagnosis, other vital and laboratory findings and complications among patients who died of COVID-19 and those who recovered from it. We directed this study to identify the present public health problem. In our study the highest proportion of our sample was between 30-39 years (18.1%) with median of 38 years and mean age of 37.9 year. Our median of age is similar to a study done at 3 tertiary hospitals in Wuhan, China (median= 38) 22 and much lower than a study done in Lombardy Region, Italy with a (median =63) 23 and also, lower than a study done on 323 hospitalized patients in china (median=61).24 In our study male percentage was a bit higher than female (51.0% vs 48.8%) which is similar to a study conducted on 107 patients infected with the novel coronavirus, SARS-CoV-2, and discharged from two hospitals in Wuhan, China (male ratio 53.3%).25 But it is lower than a study conducted in America at New York (male ratio 60.3%).26 and lower than a study conducted in a teaching hospital in Italy (male ratio 63%) 27 and also, lower than a study conducted in united states of America (male ratio 75%).28 In our study non-smokers percentage among COVID-19 were more than smokers (86.2%) similar to a study conducted on 323 COVID-19 Hospitalized Patients in Wuhan, China (88.2%)24. In our study; (31.5%) of our COVID-19 cases had comorbidities which is much less than a study done in China on 113 deceased patients with coronavirus disease2019 (49%) 29 and much less than a study conducted in in Lombardy Region, Italy (63%).23 This variation in percentages may be due to that these countries do not follow a healthy life style. There was a significant association between age and COVID-19 patient outcome, most deaths were in older age groups. This is consistent with a study done on 107 infected patients with COVID-19 in china (p value<0.001)25 and another study done also in Wuhan, China (p value<0.0001).30 One of the potential causes for this phenomenon may be that aging is associated with various structural and functional changes in the respiratory tract, resulting in reduced lung capacity, altered pulmonary remodeling, reduced regeneration and increased susceptibility to pulmonary disease 31 Or it may be due to the fact that the elderly are physically weak and have many comorbidities that not only raise the risk of pneumonia, but also affect the prognosis and immune response as new corona virus emerges 32. There was no statistical association between male and female ratio, smoking history and patient outcome, this is inconsistent with a study done in Wuhan, China to detect clinical characteristic of fatal and recovered cases of corona virus 2019 (male: female p value<0.001).33 A study done in Wuhan, China to study the factors related with disease outcome in COVID-19 hospitalized patient (male: female p value=0.517, smoking history p value= 0.018).22 In our study there was a statistically significant association between marital status and COVID-19 patient outcome (p value= 0.002), most married patients recovered and discharged 79 out of 86 (91%), while one divorce which is the only divorce patient admitted with COVID-19 and died (100%), this might be due to that absence of husband may cause emotional depression which affect the immune response of the body to fight the virus. Comorbidities, primarily cardiovascular disorders and chronic lung disorders, have been described as essential to affect mortality in hospitals in critically ill patients.34 In our study, there was no statistically significant association between having comorbidities and patient outcome (p value= 0.071), but there was a significant association between those having hypertension and COVID-19 patients' outcome (p value= 0.010), but no association between having coronary heart disease, diabetes mellitus and COVID-19 outcome. A theory is that the 2019-nCoV virus, which is linked to the ACE (angiotensin converting enzyme) inhibitors used in these patients, has produced more hypertensive patients. ACE inhibitors could indirectly increase the receptors of cell ACE2, which could be the receptors for 2019-nCoV. This is consistent with a study done on adult Wuhan, China (hypertension p value=0.000) 35  Inconsistent with a study done in United States (hypertension p value=0.31). 28 In our study there was no statistically significant association between patients using chronic drugs such as antidiabetic, heart disease drugs and antihypertensive drugs in COVID-19 patient outcome (p value= 0.303, 0.445 and 0.053 respectively). This is inconsistent with a study done in china to assess if metformin was associated with mortality in diseased hospitalized patients with COVID-19, the in-hospital mortality of 2.9% (3/104) in the metformin group was markedly decreased compared with the mortality of 12.3% (22/179) in the no-metformin group (p value= 0.01). 36 As differences in factors influencing outcomes have been observed among global populations, we hypothesize that factors such as pollution, social economic variables, genetics, population comorbidities, and availability of health status and infrastructure can all impact the COVID-19 morbidity and mortality observed across different regions. It is necessary to understand differences between the patient characteristics across different regions in order to enable better clinical awareness and allocation of medical resources. Incidence of symptoms including fever, convulsions, cough, vomiting, headache, diarrhea, rhinorrhea, cyanosis, irritability and smell loss did not vary substantially between patients who died and recovered, while sore throat, dyspnea, and fatigue were more common among those who died (p value = 0.030, 0.000, 0.000, respectively). It is easy to understand that in pulmonary disease, dyspnea also means poor prognosis and the criterion for determining COVID-19 severity. Furthermore, the vital signs data showed that most of the deceased patients had tachycardia and/or tachypnoea as well as initial saturation of blood oxygen in the death group was lower than in the recovered group. Such signs and symptoms suggested that the majority of the deceased were in serious or critical condition upon admission, and the onset of such symptoms could help physicians recognize patients at risk of poor outcome, so it is easy to understand that progressive hypoxemia also indicates poor prognosis in pulmonary diseases, so hypoxemia measures are already used to evaluate COVID-19 severity.37 Our results were consistent with a study done on adult, Wuhan (dyspnea p value=0.000 and fever p value=1.000). 35  will decrease as these patients complete their stay in hospital. Our analysis was performed in a singlecenter hospital. Therefore, a large-scale multicenter study with additional researchers is required. Currently the correct COVID-19 diagnosis and treatment methods are still under review. Early detection and adaptive monitoring of prognostic factors are important if COVID-19 is to be handled more effectively.

Conclusions:
This research found a significant association of disease outcome with age. Old patients need to be closely supervised and treated to reduce their mortality by taking appropriate medical therapy. Also, a special care, attention and monitoring should be taken inconsideration to hypertensive patients, and to patients' initial signs and symptoms including dyspnea, weakness and sore throat because they were significantly associated with disease outcome.
Patients who admitted to the hospital at severe or critical state with poor vital and laboratory findings should be followed continuously.

Authors'contributions:
Study conception, design, data analysis, data interpretation, drafting manuscript, critical revision by Dr. Iman Ahmed Mohammed. Data collection by Dr.Abbas Hasan Ali and Dr. Jaafer Naseer Al shenaty.