الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The pandemic of COVID-19 caused by SARS-CoV-2 started in December 2019 in Wuhan, China. The SARS-CoV-2 pandemic spread to Egypt in March 2020. The natural history of the pandemic is still not clear. Severity of SARS-CoV-2 ranged between mild, moderate, severe, and critical. The factors responsible for the increased susceptibility of some individuals to infection over others, rather than immunocompromised conditions, are still debated.
There are some risk factors that might affect the severity or the outcome, such as male gender, obesity, or co-morbidities (chronic lung diseases, chronic kidney disease, malignancy, diabetes, dementia or other neurological and heart conditions).
Outcomes of SARS-CoV-2 infection according to its severity could be home isolation, cure, or death. Over 30 drugs have been introduced to treat patients with SARS-CoV-2. TCZ is an anti-IL-6 receptor antibody and one of the drugs that were introduced for the treatment of COVID-19. The high cost of TCZ and the controversy about its effectiveness played a role in its shortage in Egypt. Rational selection of emergency medications during the pandemic and its economic consequences was necessary and made it reasonable to conduct this study.
The aim of the study was to describe the epidemiological features of SARS-CoV-2 infection, predict factors associated with disease severity and outcome, and compare between patients treated with TCZ combined therapy with corticosteroids alone during the first year of the pandemic.
The current retrospective study was conducted at El-Agamy isolation hospital during the period between 1st March 2020 and 28th February 2021 by collecting data of 2573 adults and 51 children with confirmed COVID-19.
All records of admitted cases were collected from electronic medical system and paper medical records of patients. The following data were collected from medical records using an Excel sheet: demographics, clinical signs, comorbidities, laboratory values, radiological features, received therapy, the evolution of clinical status, ICU admission or need for MV, complications, outcomes of infection, and duration till outcome. Follow-up for all participants was completed till reaching the final outcome or death.
All patients that were indicated to receive TCZ was classified to:
Patients who received CS alone
Patients who received CS and TCZ less than 24 hours of CS administration.
Patients who received CS and TCZ later than 24 hours of CS administration.
Then they were compared according to the infection outcome.
Descriptive data were generated for all variables.
Mean and standard deviation were used to describe if the continuous data met the normality assumption.
Frequencies and percentages summarized the categorical data. Univariate analyses using the x2 test or Fischer exact test were performed to determine the baseline differences in socio-demographic factors and health-related characteristics.
One-way Analysis of variance (ANOVA) or independent t-test for continuous data was applied for continuous variables, as appropriate.
Logistic regression was applied to evaluate the predictors of disease severity, and odds ratios (OR) and their 95% confidence intervals (CI) were calculated.
The time to death and the time to discharge were visualized by Kaplan–Meier survival curves and compared using the log-rank test.
Hazard ratios (HRs) and 95% CIs were estimated using a Cox regression model to investigate the association between mortality and the time of TCZ administration.
For all analyses significance levels were set at the 5% level, p-value <0.05 was considered statistically significant. While p > 0.05 is statistically non-significant. Statistical analysis was done using International Business Machines and Statistical Package for the Social Science (IBM© SPSS©) Statistics version 28 and R software, version 4.0.0.
Results of the present study showed that:
Patients were from 14 governorates, nearly 85% (2230 patients) were from Alexandria governorate.
During the study period, Egypt experienced two notable peaks in the distribution of COVID-19 cases: one around mid-June 2020 and the other around mid-January 2021. Remarkably, El-Agamy hospital exhibited a similar pattern, mirroring the peaks observed in the overall COVID-19 cases in Egypt.
The average CFR in El-Agamy during the study period was 27.8% compared to 4% in Egypt during the same period.
Approximately 54 % of the patients were men, the most predominant age group was 45-<65 years old. (41.1%). About 49% of COVID-19 cases (1257) had comorbid conditions.
More than two-thirds of the cases were classified as mild and moderate (27.2 % and 41.9 % respectively), while one-third of them were classified as severe to critical (3.1 % and 27.8 % respectively). About half of the patients (48.2%) had cytokine storm on admission with the same percentage being admitted to ICU with 7 days median time of ICU stay (range= 1 to 35 days).
Approximately 40% of the patients underwent MV on admission; IMV (27.8%) or NIMV (12.4%), while tracheostomy was performed on only 3.5 % of the patients and 0.5 % had received convalescent plasma.
Fever was present in only 11.5% of cases while leukopenia/lymphopenia, GGO and elevated D-dimer were found in 98.9%,72.8% and 30.2% of COVID-19 cases respective.
Males as compared to females as well as older age groups showed significantly higher percentages of comorbidities (especially hypertension, DM and heart diseases), critical cases, ICU admission, mean ventilation days and elevated D-dimer. In contrast, females showed low mean oxygen saturation and low oxygen saturation at rest.
In the present study 1776 patients (69%) were categorized as non-severe cases (mild and moderate), while 797 patients (31%) were found to be severe cases (severe and critical). Comparing severe COVID-19 patients with non-severe cases, severe cases had significantly higher mean values of age(years). most of them had 2 or more comorbid diseases, (hypertension, heart diseases and DM). Moreover, significantly higher percentages of severe cases had elevated D-dimer and experienced a cytokine storm (95.7% and 100% respectively) in comparison to the non-severe COVID-19 (0.8% and 24.9% respectively)
The important predictors significantly associated with increased severity were the presence of heart diseases (OR 53.5), hypertension and DM (OR 34 for each), cancer (21.9) (p<0.001) and age group 85+ followed by 65-<85 years (OR 7.3 and 1.8 times p=0.003 and 0.004 respectively).
As regards the outcome of the studied cases, a total of 736 (28.6%) were successfully cured and discharged,422 (16.4%) were cured but experienced complications during treatment (chest infections (8%), visual disorders (4.2%) and fungal infections (4.1%)). The least common complication was deep vein thrombosis (0. 2%). A total of 700 patients (27.2%) were referred to isolation either at home or in youth centers or in another hospital and the overall death rate reached 27.8%.
In the present study a total of 1240 COVID-19 participants experienced cytokine storm (all severe and critically ill patients; 82 and 715 respectively in addition to 443 out of the 1077 patients with moderate disease (41.1%) who were added to the patients who were eligible for TCZ administration). A total of 205 (16.5%) patients have received CSs alone without TCZ, of the remaining patients, 442 (35.6%) received TCZ within 24 hours of CSs administration (early), while 593 (47.9%) received TCZ after 24 hours (late).
Comparing outcomes of using TCZ with CSs, based on administration timing, the results illustrate that early TCZ administration showed a substantially lower mean length of stay in the ICU and mean MV days (p<0.001).
The median time to discharge significantly decreased with the administration of TCZ, either early (15 days) or late (19 days), compared to those treated with CSs alone (22 days).
Although patients who received TCZ within 24 hours of receiving CSs experienced a higher incidence of complications (52.7%) (chest infection, fungal infection, and visual problems) (51.4%, 63.8%, and 54.2%, respectively), yet. deep venous thrombosis occurred equally in all groups independent of the timing of TCZ administration
Among patients who received CSs without TCZ, 92.7% died, compared to 35.7% and 61.9% of those who received early and late TCZ, respectively
Male sex, age above 65 years old, ischemic heart disease, DM, elevated D-dimer at admission and administration of TCZ later than 24 hours (p=<0.001), were the identified significant risk factors that contributed to increased mortality.
6.2 Conclusions
The findings highlight the demographic characteristics, comorbidities, treatment strategies, and outcomes of COVID-19 patients in Egypt and can guide public health policies and clinical management strategies to reduce the burden of the disease.
Hypertension, diabetes mellitus, heart disease, cancer, and age over 65 years were the significant predictors of COVID-19 severity and mortality in this study.
Tocilizumab looks to be a highly promising therapy option for individuals with severe COVID-19.
Early administration of tocilizumab had a significant impact on clinical outcomes, risk of intubation, length of stay, and even mortality.
6.3 Recommendations
In the light of the finding of the current study, the followings recommendations are suggested for the following:
6.3.1 MoHP
Prevention and control measures of COVID-19 should be enforced and strictly applied.
Special attention should be given to COVID-19 patients who are old and having comorbid conditions particularly DM, hypertension and CVD.
Treatment protocol should be dynamically revised for moderate to severe cases and be up-to-date according to evidence-based research. In this context, TCZ timing and dosage might be revised.
In case of TCZ administration, close and continuous monitoring for possible development of complications should be applied.
Although the registration system was very successful for COVID-19 cases during the pandemics, some pitfalls might be checked such as accurate registration of presenting symptoms and signs as well as behavioral data.
Continuous analysis, monitoring and evaluation of available data is recommended associated with simultaneous informed evidence-based actions.
Attention should be paid towards the prevention and control of the highly prevalent non-communicable diseases in the community which directly and indirectly affect the population health.
It is advisable to widely implement similar sound registry system for all infectious and non-infectious diseases in health care facilities.
6.3.2 Healthcare professionals
Identification and validation of factors that predict COVID-19 disease severity and mortality is vital to improve health outcomes.
Identifying vulnerable groups for disease severity to assist decision-makers and healthcare professionals in creating better risk stratification, preventive measures, and individualized healthcare plans.
6.3.3 Community health education
Health education about safety measures is essential to avoid COVID-19 disease.
Health education to encourage and facilitate COVID-19 vaccination to prevent further spread and its related long term complications.
6.3.4 Future research recommendations
Further multicenter research is warranted to evaluate the long-term effects of COVID-19 on survivors. Such studies will inform the development of targeted interventions and strategies to mitigate the impact of future outbreaks.
Longitudinal studies with a broader range of comorbidities are recommended for post COVID-19.
Research on the use of specific cytokine measures to identify older adult at highest risk of adverse health outcomes.
A meta-analysis on the use of TCZ in moderate to severe COVID-19 cases