14-Day Outcome of Treatment Protocol Given to Patients with COVID-19 Admitted in FIC/HDU Karachi

Aims: To observe outcomes in Oxygen need after 2 weeks (p=0.000), NIV Need at admission (p=0.000) and NIV Need after 2 weeks (p=0.000). Conclusion: This study revealed various characteristics (age, supplemental oxygen requirement and comorbid conditions) of COVID-19 patients to be associated with poor outcome at 14 th day of admission. Remdesivir was found to decrease mortality, especially in patients with moderate to severe disease.


INTRODUCTION
The first case of COVID-19 infection (caused by SARS-CoV-2virus) was reported in Wuhan, China in December 2019 [1]. Within no time it spread all over the world; and was declared as global pandemic on March 11 2020 by World Health Organization (WHO) [2]. Like other countries Pakistan also faced a huge number of cases of COVID-19, with the first case being reported in Karachi on 26 th February 2020 [3]. The spread of this viral disease was so sudden and rapid that the majority of countries and their institutions were not ready to manage such a huge flow of patients and there was no predecided treatment protocol. Numerous preventative strategies and non-pharmaceutical interventions were employed to mitigate the spread of disease including careful infection control, isolation of patients, and social distancing. Despite great efforts, the numbers kept rising. Medical therapy involving corticosteroid and antivirals were encouraged as part of critical management schemes. Despite the strategic implementation of these measures, the mortality from COVID-19 kept increasing at a profoundly alarming rate. As new findings emerge, there was an urgent need for up-to-date management guidelines.
Many trials of various medications as a possible treatment were initiated in different countries. Most importantly, World Health Organization (WHO) conducted the Solidarity clinical trial for COVID-19 treatment, as world's largest randomized controlled trial enrolling 11,330 patients in 405 hospitals across 30 countries. This trial was performed to see the role of Remdesivir, Hydroxychloroquine, Lopinavir and Interferon-B1a. The main outcomes were mortality and need for assisted ventilation, which were not reduced by any of the four under trial drugs [4].
Due to unavailability of any definite cure and no specific treatment guidelines present, different institutions came up with their own treatment protocols comprising various under trial drugs, which were given to patients according to the disease severity and co-morbidities [5,6]. Similarly at HDU/FIC Karachi, we devised a standard treatment protocol with the aim to provide as much benefit to patients as possible but with no added harm. Aim of the current study was to measure the 14-day outcome of treatment protocol given to patients with COVID-19, who were admitted in HDU/FIC Karachi during the 2 nd wave of this pandemic.

Data Collection
All data regarding the medications given, oxygen demand at the time of admission, disease severity, co-morbid conditions and the outcome on 14 th day of admission was collected through the online HMIS database and from patient files on pre-approved Performa.
Patients' confidentiality was ensured.

Statistical Analysis
Collected data was analyzed using SPSS version 27.0. Qualitative variables were presented in frequency and percentage while mean and standard deviation was calculated for quantitative variable. Mean comparison was done by oneway ANOVA and dependent t-test as appropriate. Association of outcomes with qualitative variables was checked by using fisher exact/chi-square test as appropriate. P-value<0.05 were considered as significant.

RESULTS
A total of 183 patients were included in the study. There were 66.7% male and 33.3% female patients with a mean age 59.01±14.83 years. Majority (72.1%) of patients were of more than 50 years of age. Among 183 patients, 2.2% were smokers, 51.9% were hypertensive and 41% were diabetic while 5.5% had chronic obstructive pulmonary disease (COPD) and ischemic heart disease, and 3.8% were found with asthma. We found 84.7% with shortness of breath, 67.8% of patients with fever, 57.9% with cough, 17.5% with myalgia, 14.8% with fatigue, 4.9% with diarrhea, 2.7% with nausea and 1.6% with vomiting ( Fig. 1). In our study, 35% of patients expired. Detailed descriptive statistics are presented in Table-2. Out of 183 patients, 147 patients needed oxygen at the time of admission, which was reduced to 45 patients after 2 weeks, while 26 patients need NIV at admission, reduced to 21 patients on NIV after 2 weeks, as presented in Fig. 2. We found significant mean difference of age (p=0.000) while significant association of outcome was found with remdesivir given (p=0.039), cough (p=0.025), intubation after 2 weeks (p=0.006), Oxygen need at admission (p=0.000), Oxygen need after 2 weeks (p=0.000), NIV Need at admission (p=0.000) and NIV Need after 2 weeks (p=0.000). Detailed results are presented in Table-3.

DISCUSSION
Overall the mortality in this study (35%) was significantly high, probably because the bulk of the sample size comprised of elderly patients (>50 years), with > 2 comorbid conditions and with moderate to severe disease at the time of admission. In this study, the age of patients ranged from 18 to 91 year with the mean age of 59 years, which equates with the various other studies carried out on patients with COVID-19, and all of them including this study show that middle age and older patients are commonly infected and have a greater need for hospitalization as compared to the younger population [10,12,13]. The majority of our patients were males (66.7%) perhaps due to the fact that males have more chances of exposure to the infection due to spending more time out of home and with increased person-to-person interactions as compared to females, in our society. Similar finding was also noted in other studies conducted in Pakistan and China [10,11]. In a study from Indonesia [14], and the systemic literature review and meta-analysis by Ortolan et al [15], male gender was associated with higher mortality in COVID-19 patients, hypothesizing it to be due to the increased expression of ACE2 in males as compared to females [16], differences in immunological reactions and the lack of protective effect of estrogen signaling [17]. But interestingly the mortality was found to be notably higher in female patients (41%) as compared to males (32%) in this study, probably because at the time of admission 85.2% females presented with moderate and severe disease as compared to 77.9% males.
Majority (72.7%) of the patients admitted had comorbid conditions; with more than 50% having > 2 comorbidities, Hypertension, Diabetes Mellitus, Chronic Obstructive Pulmonary Disease, Ischemic Heart Disease and Asthma were the leading contributors, followed by renal, hepatic and oncologic conditions. Presence of comorbidity, especially Hypertension and Diabetes Mellitus pose a poor clinical outcome

Fig. 2. Oxygen demand of patient at admission and after 2 weeks
as the mortality in those with any comorbid condition was seen to be almost three folds higher than those without, which is in conformation with almost similar finding of a nationwide analysis conducted in China [18].
Mortality in those who received Remdesivir was slightly lesser than those who didn't (33.7% vs 36.6%), despite the fact that Remdesivir was given only to those patients who had presented with moderate to severe disease, the factor which in itself pose poor prognosis as compared to those with mild disease; indicating effectiveness of Remdesivir in reducing overall mortality, specially in moderate to severe disease, as demonstrated by other studies like that of Garcia-Vidal et al. [19]

CONCLUSION
In summary, our study revealed various characteristics of COVID-19 patients, especially age of patients, supplemental oxygen requirement and comorbid conditions, to be associated with the outcome at day 14 of admission. Remdesivir was found to decrease mortality especially in patients with moderate to severe disease.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

ETHICAL APPROVAL
As per international standard or university standard written ethical approval has been collected and preserved by the author(s).