key: cord-0852906-ecmg8kti authors: Ali, Ashaq; Siddique, Rabeea; Shi, Hongwei; Shabana; Khan, Suliman; Hu, Junjie; Zaman, Wajid; Wang, Tiejun; Dong, Men; Han, Guang title: COVID-19: Clinical aspects and therapeutics responses date: 2020-07-03 journal: Saudi Pharm J DOI: 10.1016/j.jsps.2020.06.022 sha: afe1861fef59382bfe9d04ab9d55a7ea24e8bcdd doc_id: 852906 cord_uid: ecmg8kti COVID-19 has created havoc in the world by causing thousands of demises in a short period of time. Up till now, several attempts have been made for potential therapeutics against SARS-COV2. In this retrospective, single-center study, we extracted data from 122 COVID-19, RT-PCR confirmed patients. who were treated with a new treatment strategy of lianhuaqingwen with Arbidol Hydrochloride. The patients were either asymptomatic or had mild symptoms for COVID-19 disease. Of 122 patients 21 (17.21%) patients undergo severe conditions of COVID-19, However total 111 (90.9 %) experienced mild symptoms such as fever in 93 (76.22%) patients, cough in 23 (20.17%) and muscle pain were observed in total 8 (7%) patients. Furthermore our newly applied combination (Lianhuaqingwen and Arbidol Hydrochloride) showed effects in 5-7 days for patients with mild symptoms and was found effective with 98 % recovery rate. We found the new combination is very effective against patients with mild symptoms and asymptomatic patients. Further extensive clinical investigations are required. March 11, 2020. The disease has paralyzed the world and is currently causing thousands of mortalities and morbidities worldwide (Khan et al., 2020 )(Hamza et al., 2020 . Besides transmission and biological features, previous studies have largely focused on clinical characteristics and treatment responses. At the outset, a total of 41 cases of COVID-19 reported by Huang et al. (2020) manifested fever, dry cough, myalgia, fatigue, and pneumonia, which in severe cases caused organ dysfunction (Huang et al., 2020) . Similarly, Wang et al. (2020) studied the clinical features from 138 patients and found that these patients revealed, fever (98%), fatigue (70%), and dry nonproductive cough (60 %) . In addition, Guan et al. (2020) reported that fever was developed in only 43% of COVID-19 patients on admission, however, the number increased to 88.7% during hospitalization (Guan et al., 2020) . On the other hand, studies have also focused on the recovery from COVID-19 in response to treatment that could effectively improve the symptoms. Until now, recovery responses to remdesivir and chloroquine have been reported (Studemeister et al., 2020) , (Gao et al., 2020) . At present, more potent antiviral drugs are urgent to be developed. Recently a TCM, Lianhuaqingwen (LH) have received broad adoption, particularly in treating COVID-19 cases with mild symptoms. LH in combination could potentilay relieve prime symptoms and can possibly reduce the course of the COVID-19 (Yang et al., 2020) . LH is a Chinese patent medicine composed of Herbs. The major ingredients of LH consisted of Lonicera japonica, Forsythia suspensa, Isatis indigotica , Ephedra sinica, combination with the antiviral drug for COVID-19 in asymptomatic patients or patients with mild symptoms. This retrospective, cohort, single-center study was conducted in Wuchang Fencang hospital, a makeshift hospital in Wuhan, Hubei China. Patients were admitted to the Fenceng hospital after the onset of the specified symptoms and based on selected criteria such as if an individual RT-PCR test were found positive or respiratory rate > 30 and blood oxygen saturation >93 %. All cases in this study were confirmed according to WHO recommended laboratory diagnosis guidelines. The clinical outcomes (i-e admission, length of stay, discharged, and mortality) were monitored from Feb-4, 2020 to March 17, 2020. The data including demographic data exposure history, signs and symptoms, medical history, laboratory findings, and chest computed tomographic (CT) scan were reviewed by a team of trained and experienced physicians. The date of disease onset defined from the day when the first symptoms were noticed (symptomatic patients) or the SARS-CoV-2 was detected in samples (in case of asymptomatic patients). Treatment strategies were recommended by expert medical team, mainly composed of physicians (infection department, respiratory department, endocrinology department, oncology department, traditional Chinese medicine department, and psychology department, etc.), radiologists, and laboratory doctors and the responses were observed until the termination of treatment. Informed consent was obtained from patients and permission was from the National Health Commission of China regarding the publication of this data. The severity of COVID-19 was defined by satisfying at least one of the following factors, the ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) 300 mmHg (1 mmHg ΒΌ 0.133 kPa) breathing rate > 30/min and pulse oximeter oxygen saturation at rest < 93 %, Critical illness if satisfying at least one of the following items, the respiratory failure occurred and individuals received mechanical ventilation, failure of other organs, shock, and received care in the intensive care unit. The statistical analyses were performed using software R, where different parameters were described in percentages, frequency rates, and continuous variables described via Interquartile range (IQR) mean and median. IQR Interquartile Range The median age of patients in this study was 49 years comprised of 70 (57.3 %) females and 52 (42.27%) males. Of these patients total of 8 (6.5 %) were found asymptomatic (Table.01 ). At the onset of the disease, fever 93 (76.22%), cough 23 (20.17%) muscle pain 8 (7%) were the most common symptoms ( Figure. No.1.) Less common symptoms were diarrhea, nausea, headache, and vomiting. The median duration of stay in the hospital was 18 days, and the average incubation period was 7 days. The significant alternation in laboratory findings during hospitalization was a high level of C reactive protein, lymphopenia, increases in WBC, and neutrophil count ( Both patients with mild symptoms and asymptomatic, received TCM LH Capsule in combination with Arbidol Hydrochloride tablets, with dosage and duration detail in (Table 03 ). This newly applied combination showed effects in 5-7 days for patients with mild symptoms and was found effective with 98 % recovery rate. As a result, no mechanical support was required to any of the recovered patients, during the overall course treatment. Interestingly the recovery response of the aged people and patients with other coexisting conditions such as asthma and hypertension were also noticeable. A total 47 (85%) out of 55 with the age of 60 or above were fully recovered. Similarly, in the age group of 40-60 total 61 (81.3%) patients were recovered. In our observations, this strategy with zero adverse effects (Table No 4 .) demonstrated significant recovery responses from all age groups. Moreover, the severity and complications of the COVID-19 were found in male patients as compared to female patients. However asymptomatic cases were found in females more which can be potential source of infection. Findings of the current study have shown that the treatment of COVID-19 patients with LH capsule in combination with Arbidol Hydrochloride resulted in significant recovery. Out of 122 patients, 111 were fully recovered and discharged from the hospital. however, with higher infection proportion in females, our finding confers recent results of . while disagreeing with the early report by , showed that males are most likely affected by COVID-19. More interestingly we found more asymptomatic cases in females, also reported Due to different innate immunity factors related to sex chromosomes and due to the difference in steroidal hormones (Conti P, 2020) . which could be one of the reasons for the asymptomatics characteristic of COVID-19 in females. The occurrences and risk of COVID-19 infection are similar in different ages there are no significant differences found, unlike reported previously (Huang et al., 2020) . Furthermore, the combination of LH and Aribidol Hydrochrolride we applied shows effects in 5 to 7 days (Table No .4), the symptoms reduced very rapidly where many drugs including (Arbidol Hydrochloride) fails while used as single choice or in combination with other drugs (Yueping Li, 2020) , (Ashraf et al., 2020) . It may be due to the mechanism of action of LH previously reported by (Dong et al., 2014) where LH found effective in the rapid reduction of systematic and airway inflammation by regulation of immune systems through inhibiting the release of the corresponding inflammatory factors. Moreover, recovery responses of patients aged over 60 years were also notable with 85% recovery, indicating that Arbidol's role by inhibiting the fusion of the viral envelope to the target host cell membrane and Lianghua Qin wen anti-inflammation role supportive to elderly recovery. By applying this new treatment strategy, the mild symptoms were relieved without the application of mechanical or any other therapeutics support. However, patients with bacterial infection additionally received Moxifloxacin Hydrochloride. Despite the interesting results presented in this study, the combination of TCM with western medicines should further be investigated prior to clinical recommendation for COVID-19 patients on large scale. The ratio of asymptomatic and patients with mild symptom are found more in female and are the potential source of infection. Furthermore, the combination of LH with Aribidol hydrochloride can be used as effective therapeutics against COVID-19, specifically for Patients with mild symptoms. However further studies and clinical investigations are recommended to confirm its efficacy. Approval was obtained from the National Health Commission of China , Hospital Institutional eview board approval and informed patient's consent was obtained. COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection The effect of Arbidol Hydrochloride on reducing mortality of Covid-19 patients: a retrospective study of real world date from three hospitals in Wuhan Case Series Compassionate Use of Remdesivir for Patients with Severe Covid-19. 1-10 Clinical Characteristics of Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus ( SARS-CoV-2 ): A Review and Perspective Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial The authors would like to thank collaborators members of the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China, and CAS-TWAS Fellowships.