Psychological and Clinical Predictors of COVID-19 Severity and Outcomes

Objective The present study aimed to assess the psychological and clinical determinants of coronavirus disease 2019 (COVID-19) and their association with the disease severity and outcomes. Methods This prospective study was conducted at Hayatabad Medical Complex, Peshawar-Pakistan. Admitted patients were screened for COVID-19 with reverse transcription-polymerase chain reaction (RT-PCR) and subsequently, 250 COVID positive patients were included in the final analysis. Data were obtained from the patient's medical chart; demographic and clinical characteristics were recorded using a structured questionnaire. Psychological determinants, including anxiety and depression, were measured using the Hospital Anxiety and Depression Scale (HADS). The predictors of disease severity and outcomes (recovery vs. mortality) were also studied. Results A total of 250 patients were included in this study; out of which, 193 patients recovered from this deadly virus and 57 died. Based on psychological assessment, 58.4% of the enrolled COVID-19 patients had poor HADS scores. Most of the patients who died (70.2%) had severe symptoms (poor HADS scores). Similarly, 49.6% of the total cases were observed with poor HADS, and 50.9% of those who died had severe depression. Conclusion It is concluded from the study results that psychological distress is frequent in COVID-19 patients. Age, hypertension, fatigue, abnormal respiratory rate, oxygen saturation, ferritin, and poor HADS sore were determined as the significant predictors of COVID-19 severity and outcomes.


Introduction
Since the coronavirus disease 2019 was found to be excessively transmissible, therefore, it was declared a pandemic and a public health emergency by the World Health Organization (WHO) due to its spread worldwide [1]. This viral infection has significantly impacted global activity; with the rise in death occurring each passing day, extensive social distancing and quarantine have been strongly recommended [2]. The psychological impacts of COVID-19 are evident, suggesting considerable vulnerability of the sufferers to stress. Social distancing, fear of being infected, and quarantine are some of the major psychological factors that are suggested to have a negative impact on the general population, causing some lasting consequences [2]. The severity of pathological and psychological symptoms among the affected patients varies considerably, from being asymptomatic to being critically ill with lethal complications [3]. Recent research in this domain suggests that several factors are responsible for such severity of the disease, including diabetes, smoking, and hypertension [4].
The rapid infectious rate, short latency, and fast recovery rates of the past viruses curtailed their long-term impact on physical and mental health and wellbeing [5]. Therefore, the well-adapted COVID-19 rapid and contagious attack on our human race has taken us by surprise [5]. Since by the current time, when this virus has infected more than millions of humans, it has equipped itself with more than twelve novel amino acid spikes, thus helping this deadly virus dig into and affect the soft tissues of the human lungs. The immune response to COVID-19 infection is complex. As the virus has the capability to mislead the body's defense system, leading to blood clots that occur due to cytokines storm, thus resulting in rupturing of the blood vessels that can lead to stroke and bleeding [6]. In addition, recent research reveals that several neurological systems of the human body get perturbed in the hospitalized infected COVID-19 patient, ranging from confusion, stroke to seizures, etc. [7]. Furthermore, long-term psychological impacts of COVID-19 are expected, and hence it is essential to investigate the clinically relevant psychological symptoms and their associated factors. According to the existing literature, it is suggested to be the major cause of anxiety and depression among the infected individuals and their loved ones [5]. Furthermore, anxiety and depression are known to alter human thoughts impacting feelings and influencing human behavior. The altered behavior due to anxiety and depression can loop back onto an individual's thoughts; thus, this cycle gets reverberated as a spinning wheel [7], which in turn causes changes in the human neuronal circuits and connectivity of the synapse tagging the neurons of the amygdala, hippocampus, and cortex [8,9]. Among the major contributing factors of psychological distress during COVID-19 are sociodemographic, illness-related, psychosocial, and hospital-related characteristics [10,11].
However, locally in Pakistan, there is limited evidence in relation to the psychological impacts of COVID-19 so far. Herein, the present study aimed to assess the psychological and clinical determinants of COVID-19 and their association with the disease outcomes.

Study design and ethical consideration
This prospective study was conducted at Hayatabad Medical Complex, Peshawar-Pakistan, including 250 COVID-positive cases. The study was conducted according to Helsinki rules. Ethical approval was obtained from the hospital research and ethics committee (Reference no. 518/HEC/B&PSC/2021) and written informed consent was obtained from each subject before enrollment.

Inclusion and exclusion criteria
All admitted COVID-19 positive patients were included. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed for confirmation of the COVID-19 infection. While those with cognitive impairment, i.e., conditions like dementia, delirium, or any serious psychiatric condition, were excluded from the study sample.

Biochemical estimations and data collection
The data were collected from the medical charts of the 250 COVID-19 patients; socio-demographic, and illness-related clinical characteristics using a structured questionnaire. In the illness-related clinical factors, oxygen saturation, complete blood count (CBC), electrolyte profile, liver function tests (LFTs), hematological indices, and inflammatory markers (C-reactive protein [CRP], ferritin, lactate dehydrogenase [LDH], Ddimer) were included. The outcome variable psychological distress (anxiety and depression) was assessed using the Hospital Anxiety and Depression Scale (HADS) (see Appendix; Table 4), where a total score between 0 and 7 was considered normal, 8-10 score indicates borderline abnormal, and 11-21 is considered to be abnormal with severe symptoms. Furthermore, the final outcomes included the recovery and death rate among the included patients.

Statistical analysis
The collected data was entered and analyzed on Statistical Package for the Social Sciences (SPSS) version 22.0 (IBM Corp., Armonk, NY). A Chi-square test and one-way ANOVA were used to investigate the associations between potential contributing factors and outcomes (recovery or death). An additional analysis was performed to investigate the effect of psychological determinants on the outcomes (recovery vs. death) among the COVID-19 cases. Furthermore, univariate logistic regression was used to identify the predictors of mortality among the enrolled COVID-19 patients. A p-value<0.05 was considered statistically significant.

Results
The inpatient data of 250 COVID-positive cases were included in the present study. The mean age of these patients was 54.22 ± 12.56 years; the data was stratified on the basis of hospitalization outcomes as recovery or death, as shown in Table 1. Among the clinical parameters, the blood pressure, random blood sugar (RBS), white blood cells (WBCs), platelets, ALT, oxygen saturation, ferritin, D-dimers, creatinine, prothrombin time (PT), and international normalized ratio (INR) were significantly different among the patients who recovered than those deceased (p<0.05).

Variables
Overall (  Values are given as n(%) or mean±SD.
*p-value < 0.05 will be considered as significant.
Several factors were associated with COVID-19 severity and outcomes (recovery and mortality) as per the univariate analysis. Age, HTN, fatigue, RR, SBP, DBP, oxygen saturation, RBS, ferritin, and HADS (A) were defined as the significant predictors of mortality among the enrolled COVID-19 patients (p<0.01), as shown in Table 3.

Discussion
This study was aimed to assess the prevalence of psychological distress among COVID-19 and its association with disease outcomes in terms of recovery and death. A considerable rate of psychological distress (anxiety and depression) was observed among the enrolled COVID-19 patients in the present study. Most of the patients who died had high anxiety and depression scores, indicating increased psychological distress among most severe COVID-19 cases. Our findings are in line with the existing literature [12][13][14].
Zhang et al. reported mild to moderate symptoms of anxiety and depression among 21% and 29% of patients, respectively [13]. This is also supported by a similar observational study; Bo and colleagues reported symptoms of PTSD in more than 90% of the hospitalized COVID-19 patients [14]. Symptoms of anxiety may appear minor in the beginning, but they could quickly intensify over the course of a few days [15]. Because of psychological symptoms severity in isolated and hospitalized COVID-19 patients, it appears that using psychological and psychiatric counseling methods, whether in person or through online hospital systems, can be an effective way to manage patients' clinical conditions [16].
Approximately 14.3% of the deaths are attributed to mental disorders globally. Hence it is recognized as the considerable cause of morbidity and mortality [17]. The association between mental health and COVID-19 is bi-directional, although both the facts are well-known and widely studied. That is, there is an increased risk of SARS-CoV-2 infection among patients with mental disorders [18]. Secondly, the COVID-19 patients with no previous history of psychological distress develop severe anxiety and depression, which may be due to prolonged quarantine, insufficient information, isolation, boredom, and social stigma, etc. [18,19].
Other than the psychological determinants, the patient's symptomatology, clinical profile, and management protocol were also followed. The fever appeared to be the most frequent symptom in the COVID-19 cases. Fever, cough, and fatigue appear to be the predominant symptoms among participants in several studies conducted to assess the risk factors for severe COVID-19, with fever being the most prevalent initial symptom [20,21]. Furthermore, among the laboratory parameters, oxygen saturation, ferritin, D-dimers, creatinine, PT, and INR were significantly altered, and with that, these estimations greatly varied among recovered and deceased patients (p<0.05). These findings are also supported by similar local studies [22,23].
Among the significant predictors of COVID-19 severity and outcomes were age, hypertension, fatigue, abnormal respiratory rate, oxygen saturation, blood glucose level, ferritin, and HADS. Consistent with this, a local case series from Pakistan identified age, presence of comorbidity, high neutrophil-to-lymphocyte ratio (NLR), LDH, and CRP levels as strong predictors of mortality among COVID-19 patients [22], which is also supported by other international studies [24]. But to the best of our knowledge, none of the studies focused on the psychological determinants as the potential predictors of mortality among COVID-19 patients, specifically in Pakistan.
Although the present study provides significant insight on the prevalence of psychological distress among COVID-19 patients, there are certain limitations that must be recognized. The present study did not identify the predictors or contributors of psychological distress among the COVID-19 patients. Furthermore, the sample size was small and specific to a single-center only.