Clinical and epidemiological characteristics and outcomes of Coronavirus disease-19 patients in a large longitudinal study

Introduction

The novel coronavirus infection outbreak known as Coronavirus disease (COVID)-19 emerged from Wuhan in China in December 2019.[1] The coronavirus has been spread to other countries, including Iraqi Kurdistan.[2,3] Globally by November 11, 2020, there have been 50,810,763 confirmed cases of COVID-19, including 1,263,844 deaths, reported to the World Health Organization (WHO).[4] The WHO has presented deep concern about the spread of this pandemic.[5]

Health-care systems are encountered with rapidly increasing demands due to the COVID-19 pandemic. The health systems are being overwhelmed, both directly from the coronavirus outbreak and indirectly from vaccine-preventable and treatable medical conditions. Maintaining the population’s trust in the capability of the health system is important to provide the safe essential required medical necessities and to control infection risk in medical settings. Infection control is a key step to ensuring appropriate care-seeking behavior and adherence to preventive measures.

The Kurdistan Regional Government (KRG) reported the first confirmed cases of the COVID-19 among the persons who returned from Iran in early February 2020. After that, the KRG released preventive health measures for travelers and community members. In this regard, public and private schools and universities were closed from February 26 to May 2, 2020. The curfew was applied between March 13 and April 23, 2020. The KRG has applied some other preventive measures; including reducing business hours; referring suspected cases of the COVID-19 to special medical settings; quarantining the persons with close contact with the suspected cases; and increasing awareness about preventive measures through mass media.[6]

The current disease has occurred by a different virus than previously known one. The clinical course of the COVID-19 disease caused by this new virus could be different and was not known completely.[7] The common clinical features are fever, dry cough, shortness of breath (SOB), and pneumonia. The less common clinical features are headache, diarrhea, productive cough, runny nose, and hemoptysis.[8] The clinical outcomes of the patients are different from mild to severe illnesses. The persons aged 65 years and older, smokers, and those with comorbid diseases such as diabetes mellitus (DM) and hypertension are more likely to have a severe situation.[9] The median incubation period of the COVID-19 is between 5 and 6 days, but it could take up to 24 days[10] with an uncertain period of infectivity.[11] The primary goal of controlling this virus is preventing transmission. The patients with COVID-19 show various degrees of laboratory abnormalities such as leukopenia, leukocytosis, and lymphopenia.[12]

The studies have shown that preventive measures such as lockdown and social distance are effective strategies to impede the COVID-19 outbreak across the countries.[13-15] In England, many areas with previously high case incidence reduce sharply. However, the lockdown had not the same effect in every region. For instance, in Kent, the cases were continuously increased during the lockdown, despite having the same restrictions as other regions.[16] Viruses constantly change by mutation result in new variants of a virus over time and sometimes the new variants emerge and disappear. Multiple variants of the virus caused by COVID-19 have been documented in the United States and globally during this pandemic. A new variant of Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) emerged has been responsible for up to 70% more transmissible than the previously known virus. In September 2020, the new variant represented one in four new diagnoses, while by mid-December, this rate was increased to almost two-thirds of new cases in London.[17] A similar pattern was observed in South Africa as well.[18]

The demographic and anthropometric characteristics of the diseases are different across geographic locations[19] and these differences could affect clinical outcomes. We need to analyze the data from a large investigation to find out the disease, establish a specific treatment plan, and optimize resource allocation. There are several studies about COVID-19 from countries over all continents characterizing the nature of the disease. However, we have only one small study in Iraqi Kurdistan focused on the demographic and clinical outcomes of the COVID-19 patients published at the early stage of the outbreak.[3] This study aimed to determine the clinical and epidemiological characteristics of COVID-19 patients. Besides, the association of clinical and epidemiological characteristics of COVID-19 patients with mortality rate was examined in this study.

Methods

Study design and patients

In this large follow-up study, the confirmed patients with the COVID-19 of different severities were followed up by the discharge date from three specialized COVID-19 hospitals. The patients with non-severe medical status who were not admitted to the hospitals were followed up by the mobile medical teams. The patients whose medical conditions were escalated were admitted to the hospital as well. The patients were diagnosed by a certified physician in medical settings in the Duhok governorate of Iraqi Kurdistan between March 18 and October 11, 2020. The governorates of Iraqi Kurdistan are presented in a map in Figure 1.[20] A total of 15,409 patients were diagnosed during the mentioned time. The medical doctors diagnosed the COVID-19 cases based on the WHO interim guidance for COVID-19[21] and local guidelines of the Ministry of Health. The patients were included in this study regardless of disease severity, coexisting medical conditions, and socio-demographic aspects.

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Figure 1

Map of kurdistan region with its estimated population at governorate level

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The individuals were tested for the COVID-19 for the following reasons in this region. The patients crossed the international border, had contact with a confirmed case, or became ill following visiting health facilities (suspected case). They returned from other governorates/places or they need a certificate of health to work in the private sector. Several persons were tested for the COVID-19 as a routine random screening/surveillance for the suspected cases included those persons who were in quarantine settings.

The patients who were included in this study were selected from different medical settings in the Duhok governorate. The patients who were diagnosed with severe disease were admitted to the following health settings. In early March 2020, the Burn and Plastic Surgery hospital was assigned for COVID-19. In addition, a new 100 beds hospital was made called “Lalav Infectious Diseases hospital” for treatment of the COVID-19 patients with severe and critical conditions. Thereafter, Azadi Teaching Hospital a main tertiary hospital in this region was devoted to treating the COVID-19 patients in early June 2020.

Results

The total number of COVID-19 patients was 15,409, of whom 12.3% (n = 1888) were severe/critical. The median age of the patients was 36.0 aged between 0 and 103 years; the majority were 15–49 years. The patients were males (9868, 64.0%) and females (5541, 36.0%). The incidence rate of severe/critical conditions rose with increased age groups; except for 0–14 years (11.9%). The patients with severe/critical disease were older than those with non-severe illness with a median of 9 years. The incidence rate of severe/critical patients was 8.3%, 21.1%, and 23.7% in 15–49 years, 50–64 years, and 65 and older age groups, respectively. Female and non-healthcare worker patients were more likely to have severe/critical condition; 13.0% and 12.4% compared to males and healthcare workers; 11.9% and 9.2%, respectively. Concerning pregnancy, 123 (0.08%) were infected in different trimesters (P = 0.434). The patients were from Duhok (97.8%), other Kurdish governorates (1.0%), Iraqi governorates (1.1%), and other countries (0.2%), as shown in Table 1.

Table 1 Epidemiological characteristics between non-severe and severe COVID-19 patients

The severity of the disease was more likely to be associated with certain coexisting chronic diseases such as cardiovascular diseases (18.2%) and DM (19.8%); however, chronic lung disease, renal impairment, malignancy, and immunodeficiency did not show this association [Table 2].

Table 2 Comparison of prevalence rates of coexisting disorders between non-severe and severe/critic patients

There were 8400 (54.5%) asymptomatic and 7009 (45.5%) symptomatic patients. The most common symptoms on diagnosis were fever (31.9%), cough (23.5%), loss of smell/taste (16.3%), sore throat (15.7%), SOB (9.8%), and headache (9.5%). Severe COVID-19 was more likely found in patients with SOB (11.6%), loss of appetite (2.7%), or headache (8.0%), Table 3 and Figure 2.

Table 3 Incidence rates of symptoms in patients with confirmed cases of COVID-19

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Figure 2

Prevalence rates of symptoms in patients with COVID-19

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The case fatality rate (CFR) was 1.98%, with a higher rate of aged patients. Lethality increased with age, except for the 0–14 age group (0.7%). The CFR was 0.5%, 4.0%, and 8.7% in 15–49 years, 50–64 years, and 65 and older, respectively. The median hospital stay was 4.0 days in dead patients. The mortality rate was significantly higher in non-healthcare workers compared to healthcare workers; 2.0% versus 0.6; P = 0.005. The lethality was higher in pregnant women during the second trimester (2.3%). However, the overall comparison of mortality was not statistically substantial in women with different trimesters. Regarding reasons for COVID-19 testing, there was no significant difference between patients who attended the clinic settings and those in different governorates (P = 0.258), Table 4 and Figure 3.

Table 4 Comparison of outcome of COVID-19 patients with general and epidemiological characteristics

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Figure 3

Comparison of median age between patients with different outcomes, (a) age of recovered and dead patients, (b) age of non-severe and severe/critic patients, (c) age of non-severe and severe/critic patients in recovered and dead patients, (d) hospital day of non-sever and sever/critic patients

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The patients with chronic diseases, cardiovascular diseases, or type 2 DM had a significantly higher CFR rate; 3.1%, 4.4%, and 3.4%, respectively. The patients with other coexisting disorders have not had significantly higher CFR. The asymptomatic patients had statistically higher CFR compared to symptomatic patients; 2.3% versus 1.6 (P = 0.006). Furthermore, the patients with SOB had higher CFR compared to patients without SOB; 2.8% versus 1.9%; P = 0.012 [Table 5].

Table 5 CFR I COVID-19 patients with coexisting disorders and different symptoms

The results showed that being older was the only predictor of mortality and severity in COVID-19 patients (Except for 15–49 years old). Ironically, being severe or non-severe, asymptomatic or symptomatic, or having coexisting chronic diseases were not predictors for mortality and severity in patients with COVID-19.

A similar pattern was found in the analysis of mortality predictors in patients aged ≥ 65 years old. However, older age was shown to associate with severe/critical medical conditions in patients aged ≥ 65 years old [Table 6].

Table 6 Univariate predictors of mortality in COVID-19 patients

Discussion

To the best of our knowledge, this is the first large observational study of confirmed COVID-19 patients in Iraq. The median age of the patients was 36.0 aged 0-103 years, though it is different across the world. The median age was lower compared to studies from Italy (65.0 between 18 and ≥75 years);[22] China (47.0 between 0 and ≥65 years);[24] and (56.0 between 18 and 87 years);[25] and the United States (63.0 between 0 and 107 years).[26] The lower median age of the affected persons could be due to the median age of 20 in Iraq’s population.[27]

In this study, the incidence rate of severe/critical COVID-19 patients was 12.3% and it was linked with increasing age group except for 0–14 years old. It is well documented in the literature that worse outcomes are associated with increasing age.[24,28] Overall, increasing age is associated with impaired immunity and there is an increased prevalence of comorbid diseases such as DM and hypertension. The different rates of severe/critical conditions were reported in the literature, for instance, 15.74%.[24] The studies have reported that COVID-19 patients with severe/critical conditions are older with different median years, 9 years in this study (Iraqi Kurdistan), 7 years in China.[24]

The study showed that healthcare workers (HCWs) are at risk of getting an infection by the COVID-19. In our study, 4.7% of the affected patients were HCWs. The different infection rates have been reported in the literature, 3.5%.[24] Nguyen et al.[29] followed up the general community in the UK and USA including front-line HCWs, using the self-reported technique. At the end of the follow-up time, they included 2,035,395 community individuals and 99,795 front-line healthcare workers. They recorded 5545 incident reports of a positive COVID-19 test over 34,435,272 person-days. The front-line HCWs had an increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% confidence interval [CI] 10·93–12·33). Therefore, health policymakers must pay special attention to protect the medical staff against the COVID-19 outbreak. The shortage of medical staff leads to a remarkable burden on health-care services in this region. Importantly, the risk of infection is doubled in household members of front-facing workers, in adjustment for age, gender, comorbidity, and other epidemiological factors.[30] In agreement with this study, the literature has reported similar findings.[29-31]

This study reveals that 54.5% of the patients were asymptomatic on visiting a medical doctor. Fever, cough, loss of smell/taste, sore throat, SOB, and headache are prevalent symptoms in COVID-19 patients. Those with SOB, loss of appetite, or headache are more likely to have severe/critical situations. The literature has reported that fever and cough on admission are the most prevalent symptoms in COVID-19 patients. Guan et al.[24] reported that 43.8% and 88.7% had a fever on admission and during hospitalization, respectively, and 67.8% had a cough. In addition, the patients with coexisting illness were more likely to have the severe disease compared to non-severe patients, 38.7% versus 21.0%, respectively.[24] Similar findings were reported in other parts of the words in terms of symptoms.[22,32]

The common symptoms reported by systematic reviews were fever (85.6%), cough (68.7%), and fatigue (39.4%). The frequent comorbidities are hypertension (17.4%), diabetes (3.8%), and coronary heart disease (3.8%). The critical cases with complications are 9%, intensive care unit admission is required in 7.3%, invasive ventilation in 3.4%, and mortality is 2.4%.[33] Another meta-analysis confirmed that fever and cough are the most frequent symptoms.[34]

A meta-analysis of 148 articles of 24,410 adults with confirmed COVID-19 from nine countries reported that fever 78% [95% CI 75–81%], a cough 57% [95% CI 54–60%], and fatigue 31% [95% CI 27–35%] are the most prevalent symptoms. The main concern of the authors is that a considerable percentage of patients have chronic diseases. These patients are more likely to have severe/critical disease conditions and more likely to die.

The CFR was 1.98% of 15,409 patients who were followed-up and included in this study. The CFR rate was significantly increased with increasing age, and having chronic diseases, including cardiovascular diseases, or type 2 DM. We found that asymptomatic patients had statistically higher CFR compared to symptomatic patients; 2.3% versus 1.6, respectively, except for the patients with SOB. The CFRs are different based on the coexisting chronic conditions, clinical features, and epidemiological factors. A meta-analysis of 148 articles reported a 7% mortality rate.[35]

The early findings reported from China revealed that CFR is 1.4% in laboratory-confirmed COVID-19 patients[24] and 24.0% in Italy.[22] The Italian study reported that patients aged older than 65 years (HR 3.17, 95% CI 1.84–5.44, P < 0.001), history of coronary artery disease (HR 2.93, 95% CI 1.77–4.86, P < 0.001), and active cancer (HR 2.32, 95% CI 1.15–4.67, P =0.001) as independent factors related to increased mortality risk. Zhou et al.[25] performed a multivariable regression and showed that in-hospital mortality is associated with older age (odds ratio 1·10, 95% CI 1·03–1·17), higher Sequential Organ Failure Assessment score (5·65, 2·61–12·23), and d-dimer greater than 1 mg/mL (18·42, 2·64–128·55) on admission.

In agreement with the literature, this study showed that being severe/critical or non-severe or being asymptomatic or symptomatic, or having chronic diseases are not the predictors for mortality and severity in patients with COVID-19. The older age was the only predictor of mortality and severity in COVID-19 patients. However, some other factors have been reported to be predictors for mortality. For example, Fabio et al.[22] reported that through multivariable analysis that older age, coronary artery disease, cancer, low lymphocyte count, and high Radiographic Assessment of Lung Edema score as factors independently associated with an increased risk of mortality. Other investigations have reported that older age and the presence of comorbidities are associated with an increased mortality rate in COVID-19 patients.[25,32,36]

We confirmed the previously published findings in patients from China,[37] United States,[26] and Italy.[22] They reported that older age, coexisting medical conditions such as coronary artery disease, history of hypertension, diabetes, chronic obstructive pulmonary disease, and chronic renal failure, and cancer are related to increased mortality. We back the effect of chronic diseases on increased mortality to their effect on immunity.[38] The current findings give us the utmost importance to reduce the burden of the general health system, targeting the efforts for sufficient screening of the patients at risk.

The role of age in immune system suppression must not be ignored in this disease. The countries with higher infection rates have an older population compared to the countries with low infection rates,[39] France and Italy compared to Iraq and Saudi Arabia, respectively. Adults aged 65 years and older and patients with coexisting medical conditions are more likely to have a severe-even deadly-coronavirus infection.[40] Therefore, the high infection and mortality rates in high-income countries could be due to aging and accordingly low immunity level.

The effects of aging on the immune system are presented at multiple levels. The production of B and T cells in bone marrow and thymus is decreased first. The functions of mature lymphocytes in secondary lymphoid tissues are diminished accordingly. Therefore, the aged populations unable to respond to the immune challenges as the young populations.[41]

Some other factors have been reported to associate with the mortality rate in the literature. For example, Abdulah and Hassan[42] in a global ecological study reported that the crude mortality rate is increased by raising consuming sugar-sweetened beverages and decreased by increasing fruit consumption and beans and legumes. The anti-inflammatory strategies inside foods, nutrients, or medicines are suggested as viable options for the management of COVID-19[43,44] since the coronavirus has serious inflammatory consequences for acute pneumonia in persons.[45] The human coronavirus infections cause mild to severe diseases,[3] systemic inflammation, high fever, cough, and acute respiratory tract infection, and dysfunction in internal organs leading to death.

Except for the insufficient age-related micronutrient, the nutritional status of the population has a role in the overall development of the SARS-CoV-2 infection, the clinical status, and outcomes. Therefore, the individuals need the maintenance of host macro- and micronutrient status to avoid the COVID-19 infection.[46]

The older individuals aged 60–65 years old have less ability to respond to the immune challenges and pathogens, antigens, and mitogens decreases due to immune dysregulation.[47] Characteristics of the immune system in older people are a reduction of circulating lymphocytes and loss of immune cells.[48] Besides, the older persons have reduced the production of T cells in the involved thymus. Accordingly, this decreases the function of mature lymphocytes in secondary lymphoid tissues.[41]

Conclusions

This study showed that patients with COVID-19 have a low incidence rate of severe/critical status in Iraqi Kurdistan. The incidence rate of severe/critical condition was significantly increased with increasing age and was more common in female and non-healthcare worker patients. We found that older COVID-19 patients and those with coexisting medical conditions were more likely to have severe/critical status and a high rate of CFR. Having older age was determined to be the only factor that predicted the severe/critical status and higher mortality.

Authors’ Declaration Statements

Authors’ Contributions

The corresponding author claim that all authors whom their names were reported in this study had sufficient contribution to the concept, design, review, analysis, and final approval.