The immunologic outcomes and adverse events of COVID-19 vaccine booster dose in immunosuppressed people: A systematic review.

Introduction: This study examines the efficacy and safety of three COVID-19 booster vaccines including mRNA-based vaccines (BNT162b2 (BioNTech/Pfizer) and/or mRNA-1273 (Moderna)), Non-Replicating Viral-Vector vaccines (ChAdOx1 nCoV-19 vaccine (AstraZeneca) and/or Ad26. COV2.S (Johnson & Johnson)), and Protein Subunit vaccine (SpikoGen) in immunosuppressed patients. Methods: Relevant articles were systematically searched using medical subject heading (MeSH) and keywords "COVID-19" and "booster dose" or "booster vaccine" or ''fourth dose" in the online databases of PubMed, Embase, Scopus, and Web of Science. To identify eligible studies, a two-phase screening process was implemented. Initially, three researchers evaluated the studies based on the relevancy of the title and abstract. Results: A total of 58 studies met the inclusion criteria and were included in this review. The findings suggest that booster doses offer greater protection against the disease than the primary dose. The study also compared various vaccine types, revealing that viral vector and nucleic acid vaccines outperformed inactivated vaccines. Results indicated that individuals receiving booster doses experienced superior outcomes compared to those without boosters. Vaccination against COVID-19 emerged as the most effective preventive measure against infection and symptom severity. Elevated antibody levels post-booster dose vaccination in the population signaled robust immune responses, underscoring the benefits of supplementary vaccine doses. Conclusion: This systematic review highlights preliminary evidence supporting the immunologic outcomes and safety of COVID-19 vaccine boosters in enhancing immune responses against SARS-CoV-2. However, further research is needed to determine optimal timing intervals between primary vaccination series and boosters while considering global equity issues and variant-specific considerations.

Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial.

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).

Superior Mesenteric Venous (SMV) Thrombosis Accompanied with Appendicitis in a Patient with Primary Diagnosis of Typhoid Fever.

BACKGROUND: Septic thrombophlebitis of the Superior Mesenteric Venous (SMV) is rarely accompanied by appendicitis, and symptoms are atypical, so the diagnosis is commonly delayed, resulting in it is associated with high mortality. CASE PRESENTATION: We report a case of neglected SMV septic thrombophlebitis is caused by appendicitis. The patient represented with fever, vague abdominal pain without rebound tenderness, and history of the consumption of contaminated water. Antibiotic initiated due to suspicious typhoid fever. Then typhoid fever was ruled out. Computed tomography (CT) scans revealed micro-abscess forming complicated appendicitis and the thrombus in SMV. DISCUSSION AND CONCLUSION: The patient underwent a laparoscopic appendectomy, during which retrocecal gangrened perforated appendix with a 2×2 cm abscess was drained. Based on positive culture with ESBL organism meropenem was initiated. Appendectomy and treatment with broad- -spectrum antibiotics and anticoagulation led to a full recovery.

Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir.

BACKGROUND: The role of the antiviral therapy in treatment of COVID-19 is still a matter to be investigated. Also efficacy and safety of antiviral regimens were not compared according severity of the disease. In this study the efficacy and safety of hydroxychloroquine plus atazanavir/ritonavir was compared in patients with moderate and severe COVID-19. METHODS: We prospectively evaluated the clinical outcomes of 213 patients with COVID-19 during the hospitalization course and up to 56 days after the hospital discharge. The disease was categorized to moderate and severe based on the severity of pneumonia and peripheral oxygen saturation (SpO2). The patients received the national treatment protocol containing hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus atazanavir/ritonavir (300/100 mg daily) for 7 days. Main outcomes included discharge rates at day 7, 14 and 28, 28-day mortality, rate of intensive care unit (ICU) admission and intubation, length of hospital and ICU stay and incidence of adverse events. RESULTS: The mean (SD) age of patients was 60(14) years and 53% were male. According to WHO definition, 51.64% and 48.36% of the patients had moderate (SpO2 ≥ 90%) and severe disease (SpO2 < 90%) at baseline, respectively. The discharge rate of the moderate group was significantly higher than the severe group at day 7, 14 and 28 (HR = 0.49; 95% CI: 0.35-0.69, p = < 0.001 at day 7, HR = 0.48; 95% CI: 0.35-0.66, p = < 0.001 at day 14 and HR = 0.49; 95% CI: 0.36-0.67, p = < 0.001at day 28). The 28-day mortality of the severe group was six times higher than the moderate group (HR = 6.00; 95% CI: 2.50-14.44), p = < 0.001). The need of admission in ICU for the severe group and the moderate group was 37.86% and 18.18% of the patients. Length of hospital stay was significantly shorter in the moderate group in comparison with the severe group (5 ± 4 vs. 8 ± 6 days, p < 0.001). Patients in the moderate group experienced the serious adverse events and complications less than the severe group. The discharged patients were followed up to 56 days after discharge. Some of the patients complained of symptoms such as exertional dyspnea, weakness and new-onset hair loss. CONCLUSION: Our study did not support the use of hydroxychloroquine plus atazanavir/ritonavir in patients who had SpO2 < 90% at the time of hospital admission. SpO2 was the only predictor of clinical outcomes (duration of hospital stay, discharge from the hospital and mortality) in patients treated with hydroxychloroquine plus atazanavir/ritonavir.

Interferon ß-1b in treatment of severe COVID-19: A randomized clinical trial.

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.

Pharmacotherapy Considerations in CKD Patients With COVID-19, A Narrative Review.

Treatment of coronavirus disease 2019 (COVID-19) among patients with CKD requires special pharmacotherapy considerations that are reviewed here. Literature review was done for several pharmacotherapy aspects in CKD patients including selection and modification of COVID-19 treatment, drug interactions, nephrotoxicity of drugs that are used for treatment of COVID-19 and potential risks/benefits of routine medications of CKD patients during COVID-19 pandemic. CKD patients should be treated according to local or national COVID-19 protocols as other patients. But, there is no data on using remdesivir in patients with severe CKD. Oseltamivir and ribavirin require dose modification in patients with moderate to severe CKD. Nephrolithiasis, CKD, and acute interstitial nephritis have been reported with protease inhibitors. Acute kidney injury has been reported with remdesivir in patients with severe COVID-19. Pharmacokinetic-enhanced protease inhibitors increase the concentration of some drugs such as statins, cinacalcet, steroids, calcineurin inhibitors (CNIs). Some hypothetical benefits and harms have been suggested for statins and renin-angiotensinaldosterone system inhibitors in COVID-19 patients. Continuing guideline-directed administration of these drugs is recommended. Among different immunomodulating/immunosuppressive drugs, hydroxychloroquine and CNIs are the safest ones during COVID-19. Antimetabolites are suggested to be withheld during moderate to severe COVID-19. Fluid therapy and anticoagulant prophylaxis/ treatment need special attention in CKD patients with COVID-19. CKD patients with COVID-19 are treated as other patients, with some dose modifications if needed. Be mindful for management of drug interactions as well as modification of immunosuppressive drugs in patients with moderate to severe COVID-19.

Sofosbuvir as a potential option for the treatment of COVID-19.

Sofosbuvir may be a potential option in the treatment of COVID-19 based on the similarity between the replication mechanisms of the HCV and the coronavirus. According the limited experimental evidences, it is hypothesized that sofosbuvir might be a potential option to improve care of patients with COVID-19 especially at the start of the disease and before invasion of the virus into the lung parenchymal cells. Efficacy and safety of sofosbuvir in treatment of COVID-19 may be considered in future clinical studies.

Efficacy and safety of sofosbuvir/ ledipasvir in treatment of patients with COVID-19; A randomized clinical trial.

BACKGROUND: There is no study regarding the use of SOF/LDP in treatment of COVID-19.  Objectives: In this study, the efficacy and safety of SOF/LDP were assessed in treatment of patients with mild to moderate COVID-19. METHODS: Among an open-label randomized clinical trial, 82 patients with mild to moderated COVID-19 were assigned to receive either SOF/LDP 400/100 mg daily plus the standard of care (SOF/LDP group, n=42) or the standard of care alone (control group, n=40) for 10 days. Time to clinical response, rate of clinical response, duration of hospital and ICU stay and 14-day mortality were assessed. RESULTS: Clinical response occurred in 91.46% of patients. Although rates of clinical response were comparable between the groups but it occurred faster in the SOF/LDP group than the control group (2 vs. 4 days respectively, P= 0.02). Supportive cares were provided in the medical wards for most patients but 17.07% of patients were transferred to ICU during the hospitalization course. However, durations of hospital and ICU stay were comparable between the groups.  14--day mortality rate was 7.14% and 7.5% in the SOF/ LDP and control groups respectively. No adverse effects leading to drug discontinuation occurred. Gastrointestinal events (nausea, vomiting and diarrhea) were the most common side effects (15.85%). CONCLUSION: Added to the standard of care, SOF/LDP accelerated time to the clinical response. However, rate of clinical response, duration of hospital and ICU stay and 14-day mortality were not different. No significant adverse event was detected.  More randomized clinical trials with larger sample sizes are needed to confirm the efficacy and safety of SOF/LDP in the treatment of COVID-19.

Comparing efficacy of enteral nutrition plus ranitidine and enteral nutrition alone as stress ulcer prophylaxis.

AIM: Adequacy of enteral nutrition (EN) alone as stress ulcer prophylaxis (SUP) is controversial. The aim of this study was to compare efficacy of EN alone and ranitidine plus EN as SUP. METHOD: Critically ill adults with indications to receive SUP were randomized to ranitidine 50 mg IV every 8 h plus EN (SUP) or EN alone (non-SUP) group for 7 days. Besides, endoscopy was performed at the time of recruitment and on day 7. RESULTS: During the study period, only one patient in each group of SUP and non-SUP experienced gastrointestinal bleeding. At the time of recruitment, gastric erosion and erythema were the most endoscopic findings in the SUP and non-SUP groups. These findings did not significantly change at the end of the study (p = 0.21). CONCLUSION: EN was at least effective as ranitidine plus EN as SUP.

Metoclopramide as intermittent and continuous infusions in critically ill patients: a pilot randomized clinical trial.

AIM: Metoclopramide is commonly used as a prokinetic agent in critically ill patients with enteral feeding intolerance. In this study, noninferiority of metoclopramide as intermittent versus continuous infusion was examined in critically ill patients with enteral feeding intolerance. METHODS: Forty critically ill adults patients were assigned to receive metoclopramide as either intermittent (10 mg every 6 h) or continuous (2 mg/h) infusion. Frequency of feeding intolerance and adverse effects of metoclopramide were assessed during 7 days of study. RESULTS: Number of patients with feeding intolerance during different times of the course was not different between the groups. Although not statistically significant, diarrhea and cardiac rhythm were more common in continuous than intermittent infusion group. CONCLUSION: Continuous and intermittent infusions of metoclopramide showed equivalent effectiveness in critically ill patients.