Plasmapheresis with Convalescent Plasma as a Rescue Therapy for COVID-19 Patients: A Case Series

: On December 29, 2019, an epidemic of an infectious disease caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was declared in Wuhan, China. The first case of COVID-19 in Iran (Qom Province) was reported in February 2020, and within a short period, the number of infected cases increased rapidly around the country. Evidence suggests that the levels of pro-inflammatory cytokines are high in critically ill patients, and there is a correlation between the high level of cytokines and the pathogenesis of COVID-19; consequently, COVID-19 may have complications, such as acute respiratory distress syndrome (ARDS) and even death. These inflammatory factors can lead to a cytokine storm, while counteracting this storm seems to be an effective therapeutic approach. In this case series, we reported two critically ill patients with COVID-19, undergoing plasmapheresis with convalescent plasma, corticosteroid therapy, and interferon administration.

Association Between rRT-PCR Test Results Upon Admission and Outcome in Hospitalized Chest CT-Positive COVID-19 Patients: A Provincial Retrospective Cohort with Active Follow-up

Background: The coronavirus disease 2019 (COVID-19) pandemic imposed the most devastating challenge on healthcare systems worldwide. Iran was among the first countries that had to confront serious shortages in reverse-transcriptase-polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and ventilators availabilities throughout the COVID-19 outbreak. Objectives: This study aimed to investigate the clinical course of hospitalized COVID-19 patients with different real-time RT-PCR test results during the first three weeks of the outbreak in Qazvin province, Iran. Methods: In this retrospective cohort study, patients with a positive chest computed tomography (CT) scan for COVID-19 who were admitted to all 12 hospitals across Qazvin province, Iran, between February 20 and March 11, 2020, were included and followed up until March 27, 2020. A multivariate logistic regression model was applied to compare the independent associates of death among COVID-19 patients. Then, patients were categorized into six groups based on admission to the intensive care unit (ICU) and rRT-PCR test status (positive, negative, or no test). Also, multilevel logistic regression was used to compare the odds of surviving in each group against the reference group (PCR negative patients not-received ICU) to show if the rational allocation of ICU occurred while its capacity is limited. Results: In this study, we included 998 patients (57% male; median age: 54 years) with positive chest CT scan changes. Among them, 558 patients were examined with rRT-PCR test and 73.8% tested positive. Case fatality rate (CFR) was 20.68 and 7.53% among hospitalized patients with positive and negative tests, respectively. While only 5.2% of patients were admitted to the ICU, CFR outside ICU was 17.70 and 4.65% in patients with positive and negative results not admitted to the ICU, respectively. Conclusions: Total CFR in all hospitalized COVID-19 patients in Qazvin province during the first three weeks of the pandemic was 11.7%. Also, according to the results, the main risk factors included a positive rRT-PCR test, age more than 70 years, and having two or more comorbidities or just immunodeficiency disorders. Hence, the ICU admission criteria or prioritized ICU beds allocation should be considered with more emphasis on rRT-PCR results when the capacity of ICU beds is low.

Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

Background: The emerging problem of antibiotic resistance in Pseudomonas aeruginosa is a global health concern; hence, revealing innovative therapeutic approaches (such as designing an immunogenic vaccine candidate) is needed. There is no evidence of the availability of an effective vaccine that can combat the infection caused by this microorganism. Objectives: This research was conducted to develop a potential chimeric vaccine against P. aeruginosa using reverse vaccinology approaches. Methods: The present vaccine candidate comprised outer membrane protein F and I (OprF/OprI) and PopB with appropriate linkers. After applying meticulous immune-informatics investigation, the multi-epitope vaccine was created, including helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), interferon gamma (IFN-γ), and interleukin 4 (IL-4) epitopes. Then, the physicochemical characteristics, allergenicity, toxicity, and antigenicity were analyzed. After investigating the secondary structure, the tertiary structure (3D) model was generated, refined, and validated via computational methods. Besides, the strong protein-ligand interaction and stability between the vaccine candidate and toll-like receptor 4 (TLR4) were determined via molecular docking and dynamics analyses. Moreover, in silico cloning accompanied by pET-22b (+) was used to achieve high translation efficiency. Results: Our results presumed that the chimeric-designed vaccine was thermostable and contained optimal physicochemical properties. This vaccine candidate was nontoxic and highly soluble and had stable protein and TLR4 interaction, adequately overexpressed in Escherichia coli. Overall, it could induce immune responses and repress this microorganism. Conclusions: Therefore, to inhibit Pseudomonas infections experimentally, the efficacy and safety of the vaccine design need to be validated.

Risk Factors of Oropharyngeal Candidiasis in COVID-19 Patients: A Case-control Study

Background: With the emergence and spread of coronavirus disease 2019 (COVID-19) globally, health care systems have faced the biggest challenge in recent decades. Objectives: The present study aimed to identify risk factors associated with oropharyngeal candidiasis (OPC) in COVID-19 patients. Methods: The total number of confirmed COVID-19 patients was 218 (105 cases with OPC and 113 controls without OPC). The questionnaire used in this study consisted of demographic data, treatment strategy, clinical and laboratory data, and underlying diseases collected from the onset of clinical OPC until the end of hospitalization. Results: Pseudomembranous candidiasis (77/105, 73.3%) was the most prevalent form of OPC in case patients. The majority of the cases (58.1%) and controls (58.4%) were males. Increasing age (P = 0.03) and hospitalization length (P = 0.016) were significantly associated with OPC in COVID-19 patients. Diabetes (P = 0.003), solid tumor (P = 0.019), and hypertension (P = 0.000) were the most common underlying conditions. The use of dentures (P = 0.003) and poor oral hygiene (P = 0.000) were related to OPC in the case group. Therapy with chloroquine (P = 0.012), IVIG (P = 0.001), diuretics (P = 0.000), and corticosteroid pulse therapy (P = 0.000) were significantly associated with developing OPC in case patients. Conclusions: Old age, hospitalization length, poor oral hygiene, corticosteroids use, diabetes, solid tumor, and hypertension may predispose COVID-19 patients to develop OPC.

Simple Coagulation Profile as Predictor of Mortality in Adults Admitted with COVID-19: A Meta-Analysis

Context: COVID-19 severe manifestations must be detected as soon as possible. One of the essential poor characteristics is the involvement of coagulopathy. Simple coagulation parameters, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and platelet, are widely accessible in many health centers. Objectives: This meta-analysis aimed to determine the association between simple coagulation profiles and COVID-19 in-hospital mortality. Method: We systematically searched five databases for studies measuring simple coagulation parameters in COVID-19 on admission. The random-effects and inverse-variance weighting were used in the study, which used a standardized-mean difference of coagulation profile values. The odds ratios were computed using the Mantel-Haenszel formula for dichotomous variables. Results: This meta-analysis comprised a total of 30 studies (9,175 patients). In our meta-analysis, we found that non-survivors had a lower platelet count [SMD = -0.56 (95% CI: -0.79 to -0.33), P < 0.01; OR = 3.00 (95% CI: 1.66 to 5.41), P < 0.01], prolonged PT [SMD = 1.22 (95%CI: 0.71 to 1.72), P < 0.01; OR = 1.86 (95%CI: 1.43 to 2.43), P < 0.01], prolonged aPTT [SMD = 0.24 (95%CI: -0.04 to 0.52), P = 0.99], and increased INR [SMD = 2.21 (95%CI: 0.10 to 4.31), P = 0.04] than survivors. Conclusions: In COVID-19 patients, abnormal simple coagulation parameters on admission, such as platelet, PT, and INR, were associated with mortality outcomes.

The Importance of Screening Strongyloides stercoralis Infection in Solid Organ Transplant Donors and Recipients

Background: Strongyloides stercoralis is an intestinal nematode with worldwide distribution which is endemic in tropical and subtropical areas. It is unique in its ability to complete its entire life cycle and reinfect its human host via a phenomenon called autoinfection. The majority of infections are clinically asymptomatic or can manifest with gastrointestinal symptoms, such as heartburn, bloating, diarrhea, abdominal discomfort, gastroesophageal reflux disease (GERD), or symptoms related to the penetration of larvae through skin, including dermatitis and eosinophilia. Immunosuppressed patients, such as solid organ transplant patients with untreated strongyloidiasis are at great risk of hyperinfection, dissemination syndromes, and often fatal conditions associated with strongyloidiasis. Methods: In this retrospective single-center cross-sectional study, we evaluated 157 cases (131 heart, lung, and kidney transplant recipients and 26 kidney donors) in Tehran, Iran, from March 2020 to April 2021. Demographic information including age, gender, place of birth, place of residence, underlying disease, being the donor or recipient, history of previous transplant and type of transplant, travel history to endemic regions, and seropositivity for S. stercoralis were evaluated. Results: Among 157 cases with a mean age of 38.9 years, 40 (25.5%) cases tested positive for S. stercoralis antibodies. Out of 26 donors, eight cases were seropositive, and among 131 recipients, 32 cases were seropositive. There was no significant correlation between birth place and place of residence in endemic areas and seropositivity for S. stercoralis. None of the cases showed hypereosinophilia, hyperinfection, or disseminated syndrome. Also, we found no significant correlation between the type and time of transplant, history of previous transplants, and S. stercoralis infection. Conclusions: Universal screening for S. stercoralis latent infection is important in immunosuppressed patients, especially in solid organ transplants because of the high risk of hyperinfection and disseminated syndrome, which may culminate in death. Furthermore, screening for latent strongyloides infection in donors seems to be necessary because of the possibility of strongyloides infection being transmitted from donors to recipients.

An HIV-1 Positive Woman Without Usual Immunodeficiency

Introduction: Acquired immune deficiency syndrome (AIDS) inflicts severe damage to the immune system. It transmits from one person to another through blood transfusions and vertical and sexual transmission. It should be noted that almost all papers reporting AIDS emphasized that HIV led to immune deficiency. However, this study reported the first HIV-1 seropositive woman who had an active viral load of HIV-1 without any signs or CD4 lymphocyte count depletion. Case Presentation: This study, for the first time, reported a 46-year-old HIV-1 seropositive woman without any signs and symptoms diagnosed 31 years ago by laboratory tests. Also, it is noteworthy that the patient had not received regular therapeutics during the infection period. Our serologic tests showed an active seropositive patient without any CD4 depletion. The viral load of HIV-1 was 132967.2 u/L, which was quantified by a real-time PCR assay. Also, a CBC test was performed and showed no abnormal results. Conclusions: An untreated HIV-1 positive patient without immunodeficiency is a rare condition, and we found no report of it in the literature. This article reported an HIV-1 positive patient in whom the infection was confirmed several times using the real-time PCR method.

Incidence, Risk Factors, and Timing of Macrovascular Thrombosis in the Post-COVID-19 Elderly and Assessing the Need and Duration of Extended Thromboprophylaxis: A Prospective Study

Background: COVID-19 infection causes a wide spectrum of macrovascular thrombosis, which has contributed significantly to morbidity and mortality in the elderly. Guidelines have recommended extended prophylaxis following discharge from the hospital for variable periods. The risk of thrombosis and the optimal duration of extended anticoagulation remain uncertain. Objectives: This study aimed at determining the overall incidence and timing of macrovascular thrombosis in post-COVID-19 elderly patients. It also aimed at finding out the predictive value of clinical severity, in-hospital anticoagulation, and discharge D-dimer values for the incidence of macrovascular thrombosis and overall mortality within 13 weeks following clinical recovery from acute COVID-19 infection in the elderly. Methods: In this study, 288 elderly patients with symptomatic acute COVID-19 infection discharged between August 1, 2020, and November 30, 2020, were enrolled. Details regarding the incidence of macrovascular thrombosis were collected through a telephone interview after 90 days. Data were tabulated and analyzed with IBM SPSS Statistics for Windows, Version 23.0. (Armonk, NY: IBM Corp.) Results: The number of macrovascular thrombotic events was significantly higher in group C (critical illness) than in the other two groups (17.9 vs. 1.8 and 1.1%, respectively) (P = 0.0005). Three (10.7%) patients died within 13 weeks of discharge in group C, versus one (0.6%) patient in group M (mild to moderate illness) and none in group S (severe illness) (P = 0.0005). There were two macrovascular thrombotic events in the elevated D-dimer group versus one in the reduced D-dimer group (P = 0.135). The number of deaths was high in the elevated D-dimer group [2 (8.3%) vs. 0 (0), P = 0.053]. The cumulative incidence rate of macrovascular events in the post-COVID-19 elderly cohort 13 weeks after discharge was 3.12%. Conclusions: Elderly patients with a critical illness during hospitalization due to COVID-19 and elevated D-dimer values at discharge have the maximum risk of developing macrovascular thrombosis in the post-COVID-19 period. It is reasonable to recommend extended thromboprophylaxis for at least eight weeks in the post-COVID-19 elderly.

Retapamulin: Current Status and Future Perspectives

: Retapamulin is one of the antibiotics recently developed semi-synthetically to inhibit protein synthesis in a specific manner different from other antibiotics. This pleuromutilin derivative shows magnificent anti-bacterial activity in Gram-positive pathogens, especially Staphylococcus aureus and Streptococcus pyogenes, and now it is available in ointment formulations (1%) for clinical use with negligible side effects. Despite the low potential for resistance development, antimicrobial susceptibility rates are significantly high. This is especially important when the prevalence of mupirocin-resistant strains is increasing, and the need for new alternatives is urgent. Unfortunately, due to its oxidation by cytochrome p450, this drug cannot be used systemically. However, another pleuromutilin derivative with systemic use, lefamulin, was approved in August 2019 by the US Food and Drug Administration. In addition to pharmacokinetic features, financial issues are also barriers to consider in the progress of new antimicrobials. In this review, we attempt to take a brief look at the derivatives usable in humans and explore their structures, action mode, metabolism, possible ways of resistance, resistance rates, and their clinical use to explain and highlight the valuable points of these antibiotics.