Effects of Therapeutic Modalities on Recovery and Mortality Rate of Hospitalized Patients with Covid-19

Introduction: The present study aimed to analyze the comparative effects of several types of potential compounds on the management and alleviation of hospitalized patients with COVID-19. 

Materials/ methods: This cross-sectional study included a study population of 1255 patients with COVID-19 who were admitted to hospitals affiliated with the one of the universities of medical sciences in Tehran, Iran. The data of the present study were collected using the questionnaire-based method and a researcher-made checklist. The obtained data were analyzed using SPSS software. Results: The mean age of participants in this study was 66.7 ± 16.31. The outcome of the disease was significantly associated with hospitalization, gender, education, place of residence, occupation, ethnicity, and severity of the disease. 

Conclusions: The use of anti-inflammatory and antiviral drug therapies, as well as therapeutic modalities for hospitalized patients, seems to be effective until a disease-specific drug is identified and extensive vaccinations are performed.

Currently, Coronavirus disease 2019 (COVID-19) is the most important and major health problem in the world. Coronavirus was first discovered in 1965, and in 2013 caused severe acute respiratory syndrome (SARS) in China identified by a series of gene mutations (Talebi, Nematshahi, Tajabadi, & Khosrogerdi, 2020). COVID-19 belongs to the Coronaviridae family and is responsible for the development of SARS in all countries within a short time(Jahanpeyma, Shamsi, Nejad Rahim, & Aghazadeh Sarhangipour, 2020). Covid-19 is highly lethal pneumonia and viral disease caused by SARS-CoV-2 with a high prevalence affecting all countries and territories of the world within three months ("COVID-19 Coronavirus Pandemic," December 28, 2021). To date (December 2, 2021), many drugs have been proposed for the treatment of COVID-19; however, none of them, except for a few, have been definitively approved by the scientific community. Some of these drugs are as follows; Osletamivir ("ClinicalTrials.gov (2020f). Oseltamivir covid-19," 2020; Tan et al., 2020), Chloroquine Phosphate(Fiolet et al., 2021; Gao, Tian, & Yang, 2020), Hydroxychloroquine Sulfate (Fiolet et al., 2021; Gendrot et al., 2020), Ferroquine, Amodiaquine mefloquine, Pyronaridine (PYR), Ivermectin, Colchicine, Quinine (Gendrot et al., 2020; Yao et al., 2020) Kaletra (Lopinavir/Ritonavir) (Indari, Jakhmola, Manivannan, & Jha, 2021), Remdesivir(Al-Tawfiq, Al-Homoud, & Memish, 2020)Favipiravir) Furuta, Komeno, & Nakamura, 2017), Arbidol (Umifenovir) (Li, 2020), Actemra, (Tocilizumab) (Durán-Méndez et al., 2021), Ribavirin (Xu et al., 2021) Swedac (Yadollahzadeh et al., 2021), Interferon-α (Nakhlband, Fakhari, & Azizi, 2021), Interferon-β1a (Davoudi-Monfared et al., 2020), Epoprostenol (Mulia & Luke, 2021), Dexamethasone (Coronavirus disease (COVID-19): Dexamethasone, 2020), Molnupiravir (Jayk Bernal et al., 2021), Paxlovid ("FDA grants EUA for Pfizer’s Covid-19 oral antiviral Paxlovid," 2021), Tlavperovir (Mahmoud et al., 2021), Heparin, Enoxaparin,  Rivaroxaban, Pradaxa (Dabigatran) ( COVID-19 and VTE/Anticoagulation: Frequently Asked Questions, 2021),as well as some traditional medicines such as Influenza. In addition to mentioned therapies, some other treatment modalities are also prescribed for COVID-19 patients, including monoclonal antibodies (Aleem & Slenker, 2021), Oxygen therapy (Ospina-Tascón et al., 2021), use of plasma obtained from recovered patients ("Early Use of Convalescent Plasma May Help Outpatients with COVID-19 Avoid Hospitalization," 2021; "WHO recommends against the use of convalescent plasma to treat COVID-19," 2021), Hemoperfusion (Amirsavadkouhi et al., 2021), Psychotherapy, Natural killer (NK) cells therapy - Mesenchymal stem cells (MSCs) therapy - Chimeric antigen receptor (CAR) T-cell therapy, Immunotherapy, use of monoclonal antibodies and traditional medicines such as Persian or Chinese medicine (Basiri et al., 2021). In this study, we retrospectively assessed the effect of drugs and some treatment modalities on recovery and death (two main variables) on patients with COVID-19 regarding their age, sex, educational levels, and occupation in three hospitals affiliated with the one of the universities of medical sciences in Tehran, Iran.

The present study is a cross-sectional descriptive study. The research population is patients who were admitted to three hospitals of A, B, and C affiliated to one of the universities of medical sciences in Tehran, Iran from the beginning of the pandemic, December 2019 to December 2020, and their medical records are available in these hospitals. In this study, sequential sampling was performed, meaning that the selection of qualified patients was continued until the required sample size was gathered. In this study, 1255 cases were studied and analyzed. For sampling, the interns were assigned into three sections, and each group went to specified hospitals and was given questionnaires. The medical records unit of the above-mentioned hospitals provided the required files of patients with COVID-19 for social medicine interns. The interns, while carefully studying the medical files, transferred the desired information to questionnaire forms and, in case of file incompleteness, contacted the improved patients, and while inquiring about their condition and answering their possible questions, eliminated the defects of medical records and encouraged patients for plasma donation. The map spotting process was conducted according to the location of the patients. The inclusion criteria included all hospitalized patients with a definitive diagnosis of COVID-19 whose disease was diagnosed according to clinical signs and symptoms by PCR or CT scan, and the exclusion criteria included those who, despite the presence of symptoms or the clinical signs, their PCR testing results were negative or not available, or their CT scan did not indicate the presence of disease hallmarks. The data of the present study were collected using the questionnaire-based method and a researcher-made checklist. The researcher-made checklist included ten sections, namely the demographic characteristics of patients, specific medical conditions of patients, the presence of underlying diseases, the existence of symptoms and clinical signs, laboratory tests, lung imaging results, as well as protective, supportive and therapeutic measures, general indicators related to the disease in hospitals, and the disease outcome. The validity of the designed questionnaire was confirmed by five specialists in infectious diseases, emergency, internal medicine, and surgery, and its reliability was corroborated by completing questionnaire forms by ten patients. The obtained data were entered into SPSS software version 20 in the form of code and master sheets, and data analysis was carried out. In data analysis, statistical indices of percentage, mean, standard deviation, Chi-square, T-test, and logistic regression were used. In cases where more than 25% of the data entry form was left blank or had a frequency of less than 5 or a frequency of 0, Fisher's Exact Test was used. The logistic regression test was used to examine the relationship between the studied variables and answer yes / no questions. The study protocol was approved by the Ethics Committee of Islamic Azad University of Medical Sciences (the ethical code was IR.IAU.TMU.REC.1400.341). All contributors signed written informed consent.

Table 1 shows the demographic characteristics of participants. The mean age of patients in this study was 66.7±16.31, and 67.6% of the population study were women. All hospitalized patients were residents of Tehran. Most patients were hospitalized in A Hospital (44.2%) and in the inpatient ward (78.0%). About 40.6% of patients were illiterate. They lived mostly in metropolises (54.7%), and 36.4% of female patients were homemakers. Nearly 82.4% of participants were of Persian descent. Also, 77.3% of patients were hospitalized in the COVID-19 Unit (64.9%) as an emergency, while 70.2% of them were hospitalized with moderate severity.
Table 1: Demographic characteristics of participants.

According to Table 2, the disease outcome was significantly associated with the inpatient wards; the improvement rate was significantly (p-value less than 0.001) higher in patients admitted to the internal or infectious ward of hospitals than those hospitalized in other wards. The recovery rate was significantly (p-value less than 0.001) higher in women than men and more in illiterate and homemakers in comparison with patients with academic degrees or other occupations (p-value less than 0.001). Also, patients living in metropolitan areas and from the Persian ethnicity, as well as those hospitalized in the COVID-19 ward, had more recovery rates than other patients living in rural regions, those belonging to other ethnicities, and those hospitalized in other wards (p-value less than 0.001), respectively. Notably, the recovery rate was significantly (p-value less than 0.001) higher in patients with moderate disease severity than those with severe forms of the disease. The mean age of patients who died was significantly (p-value less than 0.001) higher than patients who recovered.

Table 2: The impact of demographic variables on disease outcome.

Table 3 displays that most of the patients receivingnasal cannula, oxygen mask, Oseltamivir, Hydroxychloroquine Sulfate, Kaletra (Lopinavir / Ritonavir), Atazanavir / Ritonavir, remdesivir, Favipiravir, Arbidol, Acetaminophen, Vasoconstrictor, Anti-coagulant, Plasma, Hemoperfusion, Surfactant, Expectorant, Bronchodilator, Corticosteroids, Vitamin C, Endotracheal Tube, and Mechanical Respiration were improved and the use of these interventions was significantly associated with disease outcome.

Table 3: The effect of treatment modalities on disease outcome.

Logistic regression test showed that (table 4) the use of the endotracheal tube and mechanical respiration had a significant relationship with the disease outcome. The results indicated that the use of the endotracheal tube for hospitalized patients with COVID-19 increased the recovery rate of patients by 7.12 folds, while such a rate for those who underwent mechanical respiration was 6.21 folds.

Table 4: Logistic regression of disease outcome by drugs and treatment modalities

According to Table 5, as the logistic regression test demonstrates, in this model, the disease outcome has a significant association with educational levels, disease severity, hospitalization ward, and age. In the case of a one-unit increment in educational levels or being changed from illiterate to primary school education, the probability of recovery is increased by 1.39 folds. With a change in the disease severity from moderate to severe, the probability of recovery is decreased by 2.91 folds, and a one-unit increase in age decreases the probability of recovery by 1.03 times.

Table 5: Logistic regression of disease outcome by background variables

Impact of important demographic factors

Out of 1255 patients studied, 879 patients (70%) recovered, while 376 patients (30%) died. In a systematic review and meta-analysis that included 33 studies performed on 13,398 hospitalized patients, Macedo et al. reported a mortality rate of 11.5% for patients with moderate severity and 40.5% for patients with acute conditions (Macedo, Gonçalves, & Febra, 2021). Such a mortality rate has been reported to be 7% in China (Bauer, Brugger, Koenig, & Posch, 2021). These percentages suggest that we need to seek the causes of higher mortality in the hospitals under study. Among the independent variables analyzed, the average age of recovered patients was about 64 years, while the mean age of the deceased was about 72 years. This shows that the rate of death in our patients has increased with age. According to the reports published by the Chinese Center for Disease Control and Prevention, out of 44,672 patients, the mortality rate is 8.2% for men and 7.1% for women, which means that the mortality rate is higher in men. In a study conducted by Peter Bauer et al., they found that the risk of mortality is higher in male patients with COVID-19 than women (Bauer et al., 2021; Deng, Yin, Chen, & Zeng, 2020). Contrarily, our findings showed a significantly higher rate of death in women compared with men, indicating further need to be examined in future studies. It has been demonstrated that socioeconomic deprivation and a low level of education were consistently associated with a higher risk of COVID-19 (Concepción-Zavaleta, Coronado-Arroyo, Zavaleta-Gutiérrez, & Concepción-Urteaga, 2020). In our study, low education level was significantly associated with COVID-19 infection and death.

Healthcare workers (HCWs) are not safe and also at risk of being infected with COVID-19 (Organization, 2014). According to the reports of the Chinese Center for Disease Control and Prevention, out of 44,672 patients with positive PCR test, the percentage of infection for retirees and medical and health professionals were reported to be 21% and 4%, respectively. In this report, the number of cases working in medical centers was reported to be 1716, while the number of death was reported to be 5 individuals (0.3%) (Deng et al., 2020). In our study, the incidence of COVID-19 in retirees was 15.9%, while the percentage of infection in medical staff was 5.6%. The number of deaths in medical staff was 1.9%, indicating a 6-fold increase in comparison with the reports published by Chinses Center for Disease Control and Prevention.

Age

According to the World Health Organization (WHO), individuals in an age range between 10 and 50 years are likely to recover from the disease because the mortality rate in this age group is much less than 1%. COVID-19 patients admitted to hospitals return to normal life after spending weeks on mechanical ventilators (Balachandar et al., 2020). Moreover, the recovery responses of patients aged over 60 years to Arabidol, which inhibits the fusion of the viral envelope to the target host cell membrane (Liu et al., 2020), was remarkable by which the recovery rate was reported to be 85%. Also, a number of studies demonstrated a supportive and anti-inflammatory role of LH in elderly individuals (Khan et al., 2020).

Sex

We found that asymptomatic cases were more common in women than men, as previously reported (Noelle Breslin et al., 2020). Similarly, another study showed that most women with COVID-19 had mild symptoms and recovered more quickly than male patients. The proportion of patients who remained asymptomatic with mild symptoms was found in women more than men, indicating that men are more prone to developed symptoms (Khan et al., 2020).

The effect of drugs and some treatment modalities

Drugs

Therapeutic compounds that are currently used to date include Remdesivir, ReciGen, Chloroquine, Hydroxychloroquine, Lopinavir/Ritonavir, Favipiravir, Azithromycin, Tocilizumab, Sarilumab, corticosteroids, inhaled pulmonary dilators, such as nitrite oxide, nonsteroidal anti-inflammatory drugs, and bronchodilators. In addition, a newly-designed drug named hrsACE2 (APN01) has been discovered by researchers at Columbia University and shows effectiveness in the treatment of COVID-19 (jamalinik et al., 2020).

Vitamin D

The protective effect of vitamin D3 on reducing the severity of infectious diseases should be considered. Clinical trials with an appropriate sample size are recommended to assess the functional role of vitamin D in decreasing the severity of viral diseases of the respiratory tract (Jaafarabadi et al., 2021).

Oseltamivir

Oseltamivir is a neuraminidase inhibitor that has been suggested for the treatment of influenza A. Since COVID-19 occurred during the flu season, patients initially received Oseltamivir after being diagnosed with the flu. On the other hand, protein S, NRBD, and some parts of the virus are structurally similar to Influenza A neuraminidase; so, Oseltamivir has been suggested as an effective agent in treating COVID-19. In 2020, several clinical studies were performed on the use and efficacy of Oseltamivir in the treatment of COVID-19 ("ClinicalTrials.gov (2020f). Oseltamivir covid-19," 2020). Qi Tan et al., In a laboratory study conducted on the effect of Oseltamivir on the virus, found that the clinical use of Oseltamivir did not improve the signs and symptoms of COVID-19 patients and was not able to slow the progression of the disease (Tan et al., 2020). In our study, there was a significant difference between the number of recovered and deceased patients who received this drug in favor of the effect of this drug on recovery. However, due to the mechanism of action of this drug and numerous mutations in the virus and pandemic experiences, the use of this drug is not emphasized.

Chloroquine phosphate and hydroxychloroquine

Chloroquine is a member of the quinoline family that exerts many effects, but it is mostly prescribed for malaria. According to the literature, it has beneficial effects on adult patients with COVID-19. However, the findings of Borba et al. showed that high doses of chloroquine diphosphate in combination with azithromycin and Oseltamivir were not effective and not recommended for patients with COVID-19 (Borba et al., 2020). Laboratory studies have shown the antiviral activity of chloroquine in MERS and SARS ("Trend of the COVID-19 Pandemic in IRAN," 2020). Therefore, the use of this drug was recommended to combat this disease. A meta-analysis report found that administration of hydroxychloroquine alone significantly increased mortality in patients with COVID-19 (Fiolet et al., 2021) compared with those receiving hydroxychloroquine and azithromycin (Fiolet et al., 2021). In a review study, Pang et al. stated that hydroxychloroquine, Lopinavir / Ritonavir, Arbidol, mesenchymal stem cell therapy, Chinese traditional medicine, and glucocorticoid therapy are used for the treatment of COVID-19. Also, antiviral drugs, such as interferon, Prezcobix (Darunavir/Cobicistat), and Remdesivir, are used for patients with COVID-19 (Pang et al., 2020). Chloroquine and hydroxychloroquine are drugs with the antiviral activity that both have immunomodulatory properties that can synergistically increase the antiviral efficacy t in the body. Like other drugs, even in this emergency condition, amino chloroquine and hydroxychloroquine, which are widely used to treat malaria and rheumatic arthritis, could be used for the treatment of COVID-19 due to their anti-inflammatory and antiviral effects (Stasi, Fallani, Voller, & Silvestri, 2020). In our study, administration of chloroquine phosphate did not have a significant effect on recovery and death, but administration of hydroxychloroquine sulfate increased recovery.

Ferroquine, Amodiaquine mefloquine, Pyronaridine, and Quinine

In a laboratory study, it was shown that antimalarial drugs, such as Ferroquine, Amodiaquine mefloquine, Pyronaridine, and Quinine, were effective against SARS-CoV2 and suggested that they be effective in combating the disease and suggested that their effectiveness in combating the disease be investigated (Gendrot et al., 2020). These drugs were not used in our study.

Combinational therapy Lopinavir / Ritonavir, Atazanavir / Ritonavir

These drugs are anti-HIV drugs. In 2020, in China, a clinical trial with Lopinavir / Ritonavir was performed on hospitalized adults with COVID-19. The study showed no significant effect compared with standard care control, although fewer complications occurred. There are also studies showing successful treatment, improved physiological conditions, and reduced spread of the virus (Indari et al., 2021). A study conducted by Koo et al. demonstrated that Lopinavir / Ritonavir was not effective in adult patients admitted with severe COVID-19, suggesting further research is needed in this field (Cao et al., 2020). According to the guideline established by the National Emergency Management Plan, the main drugs used for COVID-19 include Lopinavir / Ritonavir, which is mainly used for patients with less severe symptoms and at the early stages of the disease, both at home and in the hospital. Previous experience with SARS-CoV-1 and MERS infections suggests that this drug may improve some clinical parameters of patients (Gul, Htun, Shaukat, Imran, & Khan, 2020). Our study has shown a significant effect of these two drugs, called Kaletra, on the recovery of COVID-19 patients.

Remdesivir

The drug was initially proposed to fight the Ebola virus, which mediates early termination of RNA transcription of the virus (Al-Tawfiq et al., 2020). Although this drug has been widely used, especially in our country, due to the questionable safety of this drug and the emergence of various side effects, its usage has not been approved worldwide (Guideline, 2020). Based on numerous studies, we believe that some antiviral drugs in patients with mild symptoms are promising to prevent the progression of SARS-CoV-2, and Remdesivir appears to shorten the recovery time for hospitalized patients (Stasi et al., 2020). In our study, the number of deaths was higher than the number of recovery cases, although the number of cases was not enough to be drawn a reasonable conclusion. 

Favipiravir

Favipiravir is a drug shown to be effective in treating viral diseases caused by arenaviruses, bunyaviruses, flaviviruses, filoviruses, and the Ebola virus (Dabbous et al., 2021). In several studies, the effect of this drug, if administered at the early stages of the disease, has been confirmed (Furuta et al., 2017). This drug may reduce the length of hospital stay and the need for mechanical ventilation (Dabbous et al., 2021). However, in our study, the death rate with this drug was significantly higher than in cases of recovery, and this may be due to the fact that the drug was not prescribed in the first days of the disease. However, despite reports that the effect of this drug is questionable, research is needed to be continued.

Arbidol (Omifenovir)

Arbidol is an antiviral drug used in China and Russia against the flu. In a meta-analysis study that included 15 studies, Yan et al. systematically evaluated the efficacy and quality of arbidol (Omifenovir) in the treatment of COVID-19 and concluded that the use of arbidol in the treatment of COVID-19 might be safe (Davoudi-Monfared et al., 2020). Arbidol, used to treat severe pneumonia and cytokine storm-causing viral disorders is a broad-spectrum antiviral drug that prevents the virus from entering the cell (Davoudi-Monfared et al., 2020). The findings of the present study showed that treatment of COVID-19 patients with LH capsules in combination with Arbidol hydrochloride resulted in significant improvement. In addition, the combination of LH with Arbidol hydrochloride can be used as an effective treatment option against COVID-19, especially in patients with mild symptoms. However, further studies and clinical trials are recommended to confirm its effectiveness (Khan et al., 2020). In our study, unfortunately, taking arbidol was associated with higher deaths than recovery.

Dexamethasone

The disease course has two phases, namely viral and inflammatory. According to the World Health Organization (WHO), Dexamethasone is critical in combination with standard care in the inflammatory phase (Coronavirus disease (COVID-19): Dexamethasone, 2020). In our study, the difference between improved and deceased cases was in favor of significant recovery.

Corticosteroids

The WHO recommends not to use corticosteroids in non-severe forms of COVID-19 as this treatment is of no use (World Health Organization, 2020 b). Monoclonal antibodies against cytokines as well as specific corticosteroids have been shown to be effective in counteracting and preventing cytokine storms and have been shown to improve clinical outcomes in patients with the critical stage of COVID-19 (Coronavirus disease (COVID-19): Dexamethasone, 2020).

Molnopiravir

In a clinical trial carried out on 1,433 volunteers, researchers reported that early treatment with Molnopiravir reduced hospitalization and death in high-risk and unvaccinated patients (Jayk Bernal et al., 2021).

Paxlovid

A report from Pharmaceutical Technology states that a new oral drug, Paxlovid, prevents up to 89% of hospitalization and deaths for patients 12 years and older who have a mild to moderate form of the disease or are at high risk for hospitalization and death. It also slows the progression of COVID-19 and reduces symptoms within three days ("FDA grants EUA for Pfizer’s Covid-19 oral antiviral Paxlovid," 2021).

Telaprevir

Researchers have found in a computer-based laboratory study that Telaprevir may be effective against the SARS-CoV-2 (Mahmoud et al., 2021).

Interferon-β1a or ReciGen

In a study performed on patients with definite COVID-19, it was found that using ReciGen reduced hospital stay and death (Davoudi-Monfared et al., 2020).

Interferon-α

In a systematic review, including 14 studies, the authors conclude that early administration of IFN-α may be considered a promising treatment for COVID-19 (Nakhlband et al., 2021).

Acetaminophen, Naproxen, and Ibuprofen

Acetaminophen can help reduce fever and pain, while naproxen and ibuprofen can help reduce pain and inflammation ("Which over-the-counter medications are best for coronavirus symptoms?," 2021). In our study, the use of acetaminophen was significantly higher in recovered patients than in the dead, but the use of naproxen was not significantly associated with recovery.

Anticoagulants

Factors such as senescence, masculinity, obesity, cancer, history of venous thromboembolism (VTE), comorbidities, and hospitalization in the intensive care unit are able to increase the risk of VTE. The American Society of Hematology recommends thromboprophylaxis for all patients who are hospitalized and afflicted with an acute form of COVID-19 unless there is a risk of bleeding (COVID-19 and VTE/Anticoagulation: Frequently Asked Questions, 2021). In our study, with the use of anticoagulants, the number of recoveries was significantly higher than the number of deaths. Although anticoagulants are not specific drugs for the treatment of COVID-19 patients based on results highlighted in some scientific studies, AIFA included low-molecular-weight heparins among the drugs that can be used in the treatment of COVID-19, providing useful agents to guide clinicians when prescribing ( COVID-19 - comunicazione EMA su clorochina eidrossiclorochina, 2020).

Tocilizumab (Actemra)

In a retrospective multi-centric study, the effect of Tocilizumab on 140 patients with moderate to severe forms of COVID-19 was evaluated. The study indicated that Tocilizumab in doses of 400 to 800 mg has a significant effect on reducing mortality and morbidity of patients with an acute form of COVID-19 (Durán-Méndez et al., 2021).

Plasma

The use of plasma of patients recovering from COVID-19 represents an experimental and emergency treatment previously employed for other diseases(Stasi et al., 2020).

Sovedak

In a study conducted in Iran, it was shown that Sovedak might be useful in reducing hospital stay and mortality as well as increasing patient recovery (Yadollahzadeh et al., 2021). Drugs such as Actemra (Tocilizumab), Ribavirin, Ivermectin, Sovedak, intravenous immunoglobulin, surfactant, Epoprostenol, ACE-inhibitors, quercetin, bromelain, and zinc are drugs that have been used for the treatment of COVID-19; but, in our study, neither were they used they, nor the number of cases was enough to draw any conclusion. In this study, a variety of antibiotics were used that did not show a significant effect in reducing death and increasing recovery.

Effect of some therapeutic modalities

In this study, the effect of oxygen therapy, hemoperfusion, the use of plasma from recovered patients, endotracheal tube implantation, and mechanical respiration on recovery and death was also investigated.

Oxygen therapy

In a randomized controlled trial carried out on 220 patients, Gustavo et al. found that in patients with severe COVID-19, the use of high-flow oxygen through the nasal cannula significantly reduced the need for mechanical ventilation and clinical recovery time compared to normal low-flow oxygen therapy (Ospina-Tascón et al., 2021). These results are consistent with our findings.

Hemoperfusion

In a case-series study, Savadkoohi et al. indicated that the use of hemoperfusion in controlling the adverse effects of cytokine storm following COVID-19 infection has been successful and increased the survival of COVID-19 patients (Amirsavadkouhi et al., 2021). Due to the significant difference between recovery and death with this modality in favor of increasing the number of deaths, the use of this method was approved in our study.

Plasma from recovered patients

According to Johns Hopkins University, the early use of plasma obtained from recovered patients may help reduce hospitalization of patients with COVID-19 ("Early Use of Convalescent Plasma May Help Outpatients with COVID-19 Avoid Hospitalization," 2021). However, the WHO does not recommend the transfer of plasma from these types of patients ("WHO recommends against the use of convalescent plasma to treat COVID-19," 2021). Given that in our study, the number of deaths was significantly higher than the number of recovered cases, we also do not recommend this procedure.

Molecular and immunological cell modalities

In this study, molecular and immunological cell modalities were not applied.

Mechanical respiration

In our study, the number of cases that recovered with mechanical respiration was slightly higher than expected.

According to the findings of this study and its compliance with valid scientific resources, it is suggested:

• In case of the need for oxygen therapy, especially with a cannula nasal, it should be used with extreme caution.
• Remdesivir and Favipiravir are not recommended.
• Among painkillers, acetaminophen is preferred.
• The use of expectorants is useful.
• The effectiveness of vitamin C, which is consumed in abundance, should be further investigated.
• Thromboprophylaxis is recommended for hospitalized patients.
• Dexamethasone is recommended at the inflammatory phase of COVID-19.
• Hemoperfusion is not recommended.
• Surfactant is not recommended.
• Antibiotics should not be used indiscriminately.

Acknowledgement

We should, hereby thank all medical interns who sincerely cooperated to accomplish the objectives of the project