Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Investigation of Durability of SARS-CoV-2-specific IgG and IgM Antibodies in Recovered COVID-19 Patients: A Prospective Study.

Background: Evidence on seroconversion profile of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is limited. We mainly aimed to evaluate seroconversion and persistence of virus-specific antibodies in patients infected by coronavirus disease 2019 (COVID-19). Methods: This prospective study was conducted on 118 patients with COVID-19 presentations admitted to three hospitals in Iran and recovered from the disease, during April and May 2020. Presence of COVID-19 was confirmed by Polymerase Chain Reaction (PCR) testing on nasopharyngeal swabs. Serum samples were collected at different time points, including 0-5, 6-15, 16-25, 26-35, and 36-95 days of clinical symptom onset. For measurement of SARS-CoV-2-specific IgG and IgM antibody titers, Iran's Food and Drug Administration-approved SARS-CoV-2 ELISA kits were used. Results: Serologic assay revealed that 37.3% of patients (n=44) were positive for IgM at 0-5 days interval after clinical symptom onset. This rate was 60.2% (n=71) for IgG. There were increasing IgM and IgG seroconversion rates during first 25 days of clinical symptom onset, but seropositivity started to decrease thereafter, which was more evident for IgM (17.9%) than IgG (58.9%) at the 36-95 days post symptoms appearance. In other words, it was found that 83.6% of IgM-positive and 32.9% of IgG-positive patients in the first month of clinical symptom onset became seronegative in the third month of clinical symptom onset. Conclusion: The findings demonstrated that antibody responses to SARS-CoV-2 infection were developed in recovered COVID-19 patients; however, some of them were seronegative three months after onset of relevant symptoms. Furthermore, the stability of anti-SARS-CoV-2 antibodies could also correct our expectations from COVID-19 vaccination responses.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia.

BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.

The Probable Association between Blood Groups and Prognosis of COVID-19.

BACKGROUND: We aimed to verify the association between blood group systems and prognosis of SARS-Cov-2 disease. METHODS: In this cross-sectional study, 329 patients infected with SARS-Cov-2 diagnosed based on their COVID-19 RT-PCR results and chest CT scans, were enrolled in the study. These patients were admitted to Kamkar Arab Nia Hospital, Qom, Iran from March to June 2020. Their blood groups and RH were determined, and demographic characteristics and clinical signs of patients were recorded. The patients' temperature and peripheral capillary oxygen saturation levels (SpO2) were measured. Finally, the duration of hospitalization, intubation, and death rate were also analyzed. RESULTS: The results of the patients' blood group analysis were as follows: 129(39.2%) patients had A type, 66(20.1%) B type, 21(6.4%) AB type, and 113(34.3%) O type. Of 329 patients, 297 (90.3%) had Rh antigen. The dead cases were higher in O blood type at 13 cases (11.5%). Considering the positive and negative rhesus antigen, 31 (10.4%) and 1 (3.1%) were dead respectively, but the difference was not statically significant. As for the A group, the mean of admission duration (8.4±6.1 days) was not significantly different from the B group (8.8 ±7.2 days). AB group with a mean (7.4 ±4.4 days) was not significantly different from the O group (7.8 ± 5.4 days). There was no significant difference in the duration of hospitalization in RH patients, positive or negative. B blood group showed a significant association with the time interval to return to normal oxygen levels. CONCLUSION: Blood type was not associated with COVID-19 death rate, nor was it associated with admission duration. B blood group showed a significant association with the time interval to return to normal oxygen levels.

Does vitamin D serum level affect prognosis of COVID-19 patients?

BACKGROUND: Since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic there have been contradictions and speculations about the relationship between vitamin D and COVID-19. Given that there is an association between vitamin D deficiency and some diseases - including cancer, autoimmune disease and some infectious diseases - a higher incidence and mortality rate in the vitamin-D-deficient COVID-19 population was not a surprise; conversely, some research would argue this relationship. Considering these contradictions, this study aimed to determine the relationship between prognosis and vitamin D level in cases with COVID-19. METHODS: In this cross-sectional study, 329 confirmed cases of COVID-19 - who were admitted to Kamkar-ArabNia Hospital in Qom city, Iran from March-July 2020 - were categorized into three groups according to vitamin D serum levels (ng/ml): sufficient (>30), insufficient (20-30) and deficient (<20). Prognosis was determined across the groups. RESULTS: There was a significant difference in hospital stay between patients with sufficient and insufficient vitamin D levels (P = 0.007). Adjusting vitamin D levels for confounding variables, linear regression underscored significant differences in the association between length of hospitalization and lower vitamin D levels, with a longer stay noted in insufficient groups (P = 0.002). However, there was no significant difference in the time interval to return to normal oxygen level (from SpO2 < 93%) or death rate between groups (P > 0.05). CONCLUSION: There was a significant association between hospital stay and lower serum vitamin D levels. However, the relationship between vitamin D status and death rate or the time interval to return to normal oxygen levels was not significant.

Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU.

BACKGROUND: COVID-19 is known as a new viral infection. Viral-bacterial co-infections are one of the biggest medical concerns, resulting in increased mortality rates. To date, few studies have investigated bacterial superinfections in COVID-19 patients. Hence, we designed the current study on COVID-19 patients admitted to ICUs. METHODS: Nineteen patients admitted to our ICUs were enrolled in this study. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed. Endotracheal aspirate samples were also collected and cultured on different media to support the growth of the bacteria. After incubation, formed colonies on the media were identified using Gram staining and other biochemical tests. Antimicrobial susceptibility testing was carried out based on the CLSI recommendations. RESULTS: Of nineteen COVID-19 patients, 11 (58%) patients were male and 8 (42%) were female, with a mean age of ~ 67 years old. The average ICU length of stay was ~ 15 days and at the end of the study, 18 cases (95%) expired and only was 1 case (5%) discharged. In total, all patients were found positive for bacterial infections, including seventeen Acinetobacter baumannii (90%) and two Staphylococcus aureus (10%) strains. There was no difference in the bacteria species detected in any of the sampling points. Seventeen of 17 strains of Acinetobacter baumannii were resistant to the evaluated antibiotics. No metallo-beta-lactamases -producing Acinetobacter baumannii strain was found. One of the Staphylococcus aureus isolates was detected as methicillin-resistant Staphylococcus aureus and isolated from the patient who died, while another Staphylococcus aureus strain was susceptible to tested drugs and identified as methicillin-sensitive Staphylococcus aureus. CONCLUSIONS: Our findings emphasize the concern of superinfection in COVID-19 patients due to Acinetobacter baumannii and Staphylococcus aureus. Consequently, it is important to pay attention to bacterial co-infections in critical patients positive for COVID-19.

The COVID-19 Outbreak in Iran; The First Patient with a Definite Diagnosis.

The novel coronavirus, formerly named as 2019 novel coronavirus (2019-nCov) caused a rapidly spreading epidemic of severe acute respiratory syndrome (SARS) in Wuhan, China and thereafter, progressed globally to form a pandemic of coronavirus disease 2019 (COVID-19) in numerous countries; and now confirmed cases are reported from several provinces of Iran. Now various medical centers, clinicians and researchers around the world share their data and experiences about COVID-19 in order to participate in the global attempt of controlling the pandemic. The current report investigates the clinical presentations and paraclinical findings of the first confirmed cases and mortalities in the initiation of the outbreak of COVID-19 in Iran.