Acupuncture or cupping plus standard care versus standard care in moderate to severe COVID-19 patients: An assessor-blinded, randomized, controlled trial.

Background: Non-pharmacological strategies that have been proposed by complementary medical systems, can be effective in management of COVID-19. Methods: This study was designed as a three-arm, assessor-blinded, randomized controlled trial. A total of 139 hospitalized COVID-19 patients were randomly assigned into three groups: (1) acupuncture (ACUG), (2) cupping (CUPG), and (3) control (CTRG). All participants received conventional treatment. The primary study endpoint included changes in respiratory signs including oxygen saturation (SpO2) and respiratory rate (RR). The secondary endpoints were COVID-19-related hospitalization duration and serious adverse events such as intensive care unit (ICU) admission, intubation or death, all up to day 30. Also, improvements in cough, dyspnea, chest tightness, oxygen demand, anorexia, headache, weakness, sore throat, and myalgia were evaluated. Results: Forty-two patients in ACUG, 44 patients in CUPG, and 42 patients in CTRG completed the trial. After 3 days, SpO2 and RR improved significantly in CUPG and ACUG compared with CTRG (effect size: 8.49 (6.4 to 10.57) and 8.51 (6.67 to 10.34), respectively: p<0.001). Compared with CTRG, patients in CUPG and ACUG recovered faster (mean difference: 6.58 (4.8 to 8.35) and 9.16 (7.16 to 11.15), respectively) and except for two patients in ACUG who were admitted to ICU, none of patients in ACUG or CUPG needed ICU or intubation (p<0.001 in comparison to CTRG). Amelioration of clinical COVID-19 related symptoms reached a high level of statistical significance in CUPG and ACUG in comparison with CTRG (p<0.01). Conclusion: Cupping and acupuncture are promising safe and effective therapies in management of COVID-19. Trial registration: This study was registered at Iranian Registry of Clinical Trials: IRCT20201127049504N1 (https://en.irct.ir/trial/52621).

A case report of prolonged COVID-19-positive RT-PCR for five months.

The COVID-19 gold standard assessment tool remained the RT-PCR of upper respiratory tract specimen extracted by the nasopharyngeal swab. A positive result would decrease through a three-week course and eventually be undetectable. The maximum duration of viral shedding is 83 days. Besides, COVID-19 RT-PCR remained positive for 74 days in a patient suffering from lymphoma. In this study, we have presented a 56-year-old male patient, a known case of lymphoma since 2015, who experienced many episodes of chemotherapy with a five-month positive RT-PCR COVID-19 laboratory test and finally was intubated and then died of opportunistic pulmonary infections. COVID-19 patients with concurrent lymphoma failed to remove the virus thoroughly, despite providing appropriate treatment regimens.

Effect of nanocurcumin supplementation on the severity of symptoms and length of hospital stay in patients with COVID-19: A randomized double-blind placebo-controlled trial.

It has been more than a year since the outbreak of COVID-19, and it is still the most critical issue of the healthcare system. Discovering effective strategies to treat infected patients is necessary to decrease the mortality rate. This study aimed to determine the effects of nanocurcumin on the severity of symptoms and length of hospital stay (LOS) in COVID-19 patients. Forty-eight COVID-19 patients were randomly assigned into nanocurcumin (n = 24) and placebo (n = 24) groups receiving 160 mg/day nanocurcumin or placebo capsules for 6 days. Mean differences of O2 saturation were significantly higher in patients who received nanocurcumin supplements (p = 0.02). Also, nanocurcumin treatment significantly reduced the scores of domains 3 and 4 and the total score of Wisconsin Upper Respiratory System Survey (WURSS-24), indicating milder symptoms in the treatment group (p = 0.01, 0.03, and 0.01 respectively). Besides, the LOS in curcumin groups was lower than in the placebo group, although the difference was not statistically significant (6.31 ± 5.26 vs. 8.87 ± 8.12 days; p = 0.416). CBC/differentiate, hs-CRP level and the pulmonary involvement in CT scan were not different between the two groups. As nanocurcumin can be effective in increasing O2 saturation and reducing the severity of symptoms in COVID-19 patients, it could probably be used as a complementary agent to accelerate the recovery of patients.

Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial.

OBJECTIVE: The goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D3 (25(OH)D3) in improving vitamin D status in vitamin D-deficient/vitamin D-insufficient patients infected with the SARS-CoV-2 (COVID-19) virus. METHODS: This is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review]. RESULTS: A total 106 hospitalized patients who had a circulating 25(OH)D3 concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D3 had a sufficient circulating 25(OH)D3 concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D3 concentration during the 2-month follow-up. We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D3 group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D3 was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality. CONCLUSION: Our analysis indicated that oral 25(OH)D3 was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D3 may be needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in patients with COVID-19.

Efficacy of Persian medicine herbal formulations (capsules and decoction) compared to standard care in patients with COVID-19, a multicenter open-labeled, randomized, controlled clinical trial.

Persian medicine has recommended clinical experiences and proper herbal remedies for prevention and treatment of microbial infections and respiratory diseases. An open-label, randomized, controlled, multicenter trial was conducted at five hospitals in Tehran and Isfahan provinces of Iran on 358 hospitalized adult patients. A total of 174 patients received standard care and 184 received herbal remedies (polyherbal decoction every 8 hr and two herbal capsules every 12 hr) plus standard care for 7 days. The primary clinical endpoint was the duration of hospital stay, and secondary outcomes were clinical improvement of symptoms based on self-assessment questionnaire. Results demonstrated that these natural decoction and capsules treatment plus routine care significantly decreased duration of hospital dyspnea (3.291 day vs. 6.468 days), accelerated clinical improvement, and decreased symptoms such as dry cough, dyspnea, muscle pain, headache, fatigue, anorexia, chills, runny nose, sputum cough, and vertigo in the treatment group compared with standard-care group. Significant effects of these polyherbal formulations on improving the symptoms of COVID-19 could be incredibly promising for managing this pandemic with acceptable tolerability.

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial.

INTRODUCTION: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients. METHODS: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day-1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population. RESULTS: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study. CONCLUSIONS: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.

Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial.

As no specific pharmacological treatment has been validated for use in coronavirus disease 2019 (COVID-19), we aimed to assess the effectiveness of azithromycin (AZM) in these patients at a referral centre in Iran. An open-label, randomised controlled trial was conducted on patients with laboratory-confirmed COVID-19. A total of 55 patients in the control group receiving hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) were compared with 56 patients in the case group who in addition to the same regimen also received AZM. Patients with prior cardiac disease were excluded from the study. Furthermore, patients from the case group were assessed for cardiac arrythmia risk based on the American College of Cardiology (ACC) risk assessment for use of AZM and HCQ. The main outcome measures were vital signs, SpO2 levels, duration of hospitalisation, need for and length of intensive care unit admission, mortality rate and results of 30-day follow-up after discharge. Initially, there was no significant difference between the general conditions and vital signs of the two groups. The SpO2 levels at discharge were significantly higher, the respiratory rate was lower and the duration of admission was shorter in the case group. There was no significant difference in the mortality rate between the two groups. Patients who received AZM in addition to HCQ and LPV/r had a better general condition. HCQ+AZM combination may be beneficial for individuals who are known to have a very low underlying risk for cardiac arrhythmia based on the ACC criteria.

Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: Species identification and antifungal susceptibility pattern.

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients. PATIENTS AND METHODS: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients.