The use of remdesivir in patients with COVID-19.

Remdesivir has appeared to be the most effective medication against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is broadly administered to coronavirus disease 2019 (COVID-19) patients around the world. Remdesivir is an RNA polymerase inhibitor with a broad spectrum of antiviral activities against RNA viruses in in-vitro and in-vivo models of SARS-CoV, the Middle East respiratory syndrome (MERS), and SARS-CoV-2. Remdesivir is the first Food and Drug Administration (FDA) approved anti-SARS-CoV-2 treatment for adult and pediatric patients and has been used for not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death. However, questions have been raised about the value of remdesivir in treating COVID-19, and governing bodies worldwide have been hesitant to approve this medication. Nevertheless, in the context of the public health emergency and the urgent need for effective treatments for patients with COVID-19, remdesivir has been approved by several authorities worldwide. Here, we discuss the characteristics and applications of remdesivir, and various challenging studies with different outcomes about its efficacy are also reviewed.

Pathophysiology and Management of Tongue Involvement in COVID-19 Patients.

Evaluate the lingual manifestations of COVID-19, and provide a clinical guide in managing these symptoms. Electronic databases, such as PubMed/Medline, and Scopus were searched until November 1, 2020, and only randomized controlled trials, cross-sectional and cohort studies, as well as case reports and series, and review articles in English were considered. A total of 40 studies were included in this study. Lingual involvement has been extensively reported in patients with coronavirus disease 2019 (COVID-19). The most common features of lingual involvements were red or light red, yellow coating, and greasy coating tongue, though other complications, such as pale, purple, white coating, grayish-black coating, rough, tender, puffy, spotty, prickles, fissured, and tooth-marked tongue was also reported. Poor oral hygiene, opportunistic infections (OIs), medications, and hyper-inflammatory response to infection are the most common predisposing factors for the onset of oral lesions in patients with COVID-19. In conclusion, the current review described the lingual manifestations of COVID-19, and as oral complaints are relatively common in COVID-19 patients, an intraoral examination should be conducted in all suspected cases of SARS-CoV-2 infection.

SARS-CoV-2 Omicron (B.1.1.529) Variant: A Challenge with COVID-19.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there have been multiple peaks of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus virus 2) infection, mainly due to the emergence of new variants, each with a new set of mutations in the viral genome, which have led to changes in the pathogenicity, transmissibility, and morbidity. The Omicron variant is the most recent variant of concern (VOC) to emerge and was recognized by the World Health Organization (WHO) on 26 November 2021. The Omicron lineage is phylogenetically distinct from earlier variants, including the previously dominant Delta SARS-CoV-2 variant. The reverse transcription-polymerase chain reaction (RT-PCR) test, rapid antigen assays, and chest computed tomography (CT) scans can help diagnose the Omicron variant. Furthermore, many agents are expected to have therapeutic benefits for those infected with the Omicron variant, including TriSb92, molnupiravir, nirmatrelvir, and their combination, corticosteroids, and interleukin-6 (IL-6) receptor blockers. Despite being milder than previous variants, the Omicron variant threatens many lives, particularly among the unvaccinated, due to its higher transmissibility, pathogenicity, and infectivity. Mounting evidence has reported the most common clinical manifestations of the Omicron variant to be fever, runny nose, sore throat, severe headache, and fatigue. This review summarizes the essential features of the Omicron variant, including its history, genome, transmissibility, clinical manifestations, diagnosis, management, and the effectiveness of existing vaccines against this VOC.

Prevalence of Psychological Distress and Posttraumatic Stress Symptoms and Associated Factors in Hospitalized Iranian COVID-19 Patients.

Objectives: To investigate the prevalence of psychiatric symptoms/distress and posttraumatic stress (PTS) and associated factors among inpatients with COVID-19 before discharge from the hospital. Methods: This cross-sectional study was conducted in two teaching referral hospitals in Babol, Iran from July to November 2020. The subjects were inpatients diagnosed with COVID-19 who were clinically stable. Before their discharge from the hospital, the patients completed three questionnaires: demographic data, Brief Symptom Inventory, and Primary Care Post Traumatic Stress Disorder Screen for Diagnostic and Statistical Manual-5. Results: The subjects were 477 inpatients diagnosed with COVID-19 including 40 (8.4%) admitted to intensive care units. Their average age was 60.5±17.9 years; 53.9% were female. Most had symptoms of significant psychological distress (96.0%) and PTS (8.1%) prior to discharge. A higher level of education (-0.18; standard error (SE) = 0.05; p < 0.001) was a negative predictor of psychiatric distress. The admission to intensive care units (0.86; SE = 0.08; p< 0.001) was a positive predictor of psychiatric distress. Conclusions: Most COVID-19 inpatients suffered significant psychiatric distress and PTS symptoms before discharge. Appropriate mental health crisis interventions are recommended for COVID-19 patients during hospitalization.

A review of the potential neurological adverse events of COVID-19 vaccines.

Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG) and Guillain-Barre syndrome (GBS). The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell's palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.

The role of cytokines and their antagonists in the treatment of COVID-19 patients.

The coronavirus disease 2019 (COVID-19) has various presentations, of which immune dysregulation or the so-called cytokine storm syndrome (COVID-CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID-19 infections, caused by the excessive release of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, tumour necrosis factor, granulocyte-macrophage colony-stimulating factor, and interferon-gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin-6 receptor blocker approved to treat severe COVID-19 infections.

Evaluation of Time-Varying Biomarkers in Mortality Outcome in COVID-19: an Application of Extended Cox Regression Model

Background: COVID-19 pandemic has created many challenges for clinicians. The monitoring trend for laboratory biomarkers is helpful to provide additional information to determine the role of those in the severity status and death outcome. Objective: This article aimed to evaluate the time-varying biomarkers by LOWESS Plot, check the proportional hazard assumption, and use to extended Cox model if it is violated. Methods: In the retrospective study, we evaluated a total of 1641 samples of confirmed patients with COVID-19 from October until March 2021 and referred them to the central hospital of Ayatollah Rohani Hospital affiliated with Babol University of medical sciences, Iran. We measured four biomarkers AST, LDH, NLR, and lymphocyte in over the hospitalization to find out the influence of those on the rate of death of COVID-19 patients. Results: The standard Cox model suggested that all biomarkers were prognostic factors of death (AST: HR=2.89, P<0.001, Lymphocyte: HR=2.60, P=0.004, LDH: HR=2.60, P=0.006, NLR: HR=1.80, P<0.001). The additional evaluation showed that the PH assumption was not met for the NLR biomarker. NLR biomarkers had a significant time-varying effect, and its effect increase over time (HR(t)=exp (0.234+0.261×log(t)), p=0.001). While the main effect of NLR did not show any significant effect on death outcome (HR=1.26, P=0.097). Conclusion: The reversal of results between the Cox PH model and the extended Cox model provides insight into the value of considering time-varying covariates in the analysis, which can lead to misleading results otherwise.

Do we miss rare adverse events induced by COVID-19 vaccination?

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused many complications, the invention of coronavirus disease 2019 (COVID-19) vaccines has also brought about several adverse events, from common side effects to unexpected and rare ones. Common vaccine-related adverse reactions manifest locally or systematically following any vaccine, including COVID-19 vaccines. Specific side effects, known as adverse events of particular interest (AESI), are unusual and need more evaluation. Here, we discuss some of the most critical rare adverse events of COVID-19 vaccines.

Do we miss rare adverse events induced by COVID-19 vaccination?

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused many complications, the invention of coronavirus disease 2019 (COVID-19) vaccines has also brought about several adverse events, from common side effects to unexpected and rare ones. Common vaccine-related adverse reactions manifest locally or systematically following any vaccine, including COVID-19 vaccines. Specific side effects, known as adverse events of particular interest (AESI), are unusual and need more evaluation. Here, we discuss some of the most critical rare adverse events of COVID-19 vaccines.

One-year prevalence and the association between SARS-CoV-2 cycle threshold, comorbidity and outcomes in population of Babol, North of Iran (2020-2021)

Background: The present study aimed to investigate the one-year prevalence of SARS-CoV-2, common comorbidities and demographic information among negative- and positive rRT-PCR in health care workers (HCW), hospitalized and outpatients. Also, the association between SARS-CoV-2 cycle threshold (Ct) and the outcomes of patients were analyzed in Babol, northern Iran. Methods: This large retrospective cross-sectional study was performed between March 2020 and March 2021. The records of 19232 hospitalized, outpatients and HCW suspected to COVID-19 were collected from teaching hospitals in the North of Iran. Results: Out of the 19232 suspected to COVID-19 patients, 7251 (37.7%) had a positive rRT-PCR result;652 (9%), 4599 (63.4%) and 2000 (27.6%) of those were categorized as HCW, hospitalized and outpatients, respectively. Moreover, between the hospitalized and the outpatient group, 10.2 and 0.8% cases died, whereas no death cases were reported in the HCW. Furthermore, it seems that death rate was significantly different between the three groups of Ct value, the highest mortality in those with Ct between 21 and 30 (group B=7.6%) and the lowest in the group with the highest Ct (between 31 and 40 = 5.5%) (p<0.001). Conclusion: In summary, 37.7% of cases were positive for SARS-CoV-2;of which, 63.4, 27.6 and 9% were hospitalized, outpatients and HCW, respectively. With regard to the mortality rate in hospitalized patients and the significant association with Ct under 20 and 30, it seems that the early detection and the initial quantification of SARS-CoV-2 in the first week of the conflict and therapeutic considerations to reduce the relative load can reduce the mortality rate.

Prognostic accuracy of inflammatory markers in predicting risk of ICU admission for COVID-19: application of time-dependent receiver operating characteristic curves.

OBJECTIVE: Intensive care unit (ICU) admission occurs at different times during hospitalization among patients with COVID-19. We aimed to evaluate the time-dependent receive operating characteristic (ROC) curve and area under the ROC curve, AUC(t), and accuracy of baseline levels of inflammatory markers C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in predicting time to an ICU admission event in patients with severe COVID-19 infection. METHODS: In this observational study, we evaluated 724 patients with confirmed severe COVID-19 referred to Ayatollah Rohani Hospital, affiliated with Babol University of Medical Sciences, Iran. RESULTS: The AUC(t) of CRP and NLR reached 0.741 (95% confidence interval [CI]: 0.661-0.820) and 0.690 (95% CI: 0.607-0.772), respectively, in the first 3 days after hospital admission. The optimal cutoff values of CRP and NLR for stratification of ICU admission outcomes in patients with severe COVID-19 were 78 mg/L and 5.13, respectively. The risk of ICU admission was significantly greater for patients with these cutoff values (CRP hazard ratio = 2.98; 95% CI: 1.58-5.62; NLR hazard ratio = 2.90; 95% CI: 1.45-5.77). CONCLUSIONS: Using time-dependent ROC curves, CRP and NLR values at hospital admission were important predictors of ICU admission. This approach is more efficient than using standard ROC curves.

A Large Retrospective Study of Epidemiological Characteristics of COVID-19 Patients in the North of Iran: Association between SARS-CoV-2 RT-PCR Ct Values with Demographic Data

Objectives To avoid worsening from mild, moderate, and severe diseases and to reduce mortality, it is necessary to identify the subpopulation that is more vulnerable to the development of COVID-19 unfavorable consequences. This study aims to investigate the demographic information, prevalence rates of common comorbidities among negative and positive real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) patients, and the association between SARS-CoV-2 cycle threshold (Ct) at hospital admission, demographic data, and outcomes of the patients in a large population in Northern Iran. Methods This large retrospective cross-sectional study was performed from 7 March to 20 December 2020. Demographic data, including gender, age, underlying diseases, clinical outcomes, and Ct values, were obtained from 8,318 cases suspected of COVID-19, who were admitted to four teaching hospitals affiliated to Babol University of Medical Sciences (MUBABOL), in the north of Iran. Results Since 7 March 2020, the data were collected from 8,318 cases suspected of COVID-19 (48.5% female and 51.5% male) with a mean age of 53 ± 25.3 years. Among 8,318 suspected COVID-19 patients, 3,250 (39.1%) had a positive rRT-PCR result;1,632 (50.2%) patients were male and 335 (10.3%) patients died during their hospital stay. The distribution of positive rRT-PCR revealed that most patients (464 (75.7%)) had a Ct between 21 and 30 (Group B). Conclusion Elderly patients, lower Ct, patients having at least one comorbidity, and male cases were significantly associated with increased risk for COVID-19-related mortality. Moreover, mortality was significantly higher in patients with diabetes, kidney disease, and respiratory disease.

COVID-19 vaccination challenges: A mini-review.

The emergence of SARS-CoV-2 has led to the infection of many people across the globe, over six million deaths, and has placed an unprecedented burden on public health worldwide. The pandemic has led to the high-speed development and production of vaccines against the COVID-19, as vaccines can end the pandemic. At the beginning of the program, vaccinations were initially targeted only at high-risk groups, such as the elderly, those with comorbidities, or healthcare workers. Although most of the mentioned populations have received the two recommended doses, limited resources have left many authorities with an effective vaccine undersupply. Therefore, policies have been implemented to manage the available doses of the vaccines more efficiently. As there is no universally agreed consensus on this topic, we discuss the different recommendations and guidelines regarding the time interval between the two vaccine doses and explain the different scenarios for applying the two doses.

Breakthrough SARS-CoV-2 infections after vaccination: a critical review.

At the beginning of the current pandemic, it was believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection would induce lifelong immunity and that reinfections would be unlikely. However, after several cases of reinfection were documented in previously infected patients, this was understood to be a false assumption, and this waning humoral immunity has raised significant concerns. Accordingly, long-term and durable vaccine-induced antibody protection against infection have also become a challenge, as several breakthroughs of COVID-19 infection have been identified in individuals who were fully vaccinated. This review discusses the current evidence on breakthrough COVID-19 infections occurring after vaccination.

COVID‐19 vaccine‐related new‐onset lichen planus

Coronavirus disease 2019 (COVID‐19) vaccines significantly impacted world health and well‐being. However, various adverse events have been observed following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. Cutaneous reactions have been prevalent following many vaccines, including COVID‐19 vaccines. Here, we present a case of new‐onset lichen planus in a patient who received the COVID‐19 vaccine at the same time as being infected with SARS‐CoV‐2. A 52‐year‐old woman presented to the clinic with extensive pruritic skin lesions. The eruptions had appeared a week after her second dose of the Sinopharm COVID‐19 vaccine. She mentioned a history of SARS‐CoV‐2 infection approximately 10 days following the first dose of her vaccine, causing a 1‐month delay in getting the second dose. Her past medical history was not significant. On examination, erythematous and squamous papules were demonstrated predominantly on the extremities, including inguinal and axillary folds. Moreover, desquamation of the lips was visible, and buccal lesions were also found. After consultation with a dermatologist, a skin biopsy was indicated for the patient, but she refused to undergo the procedure. Therefore, considering the typical appearance of the eruptions, lichen planus was suspected, for which she was treated with oral antihistamines and topical corticosteroids. Dermatologists should be aware of the probability of new‐onset or exacerbated mucosal skin disorders due to the vast range of cutaneous adverse events following COVID‐19 vaccination and actively monitor susceptible patients.

SARS-CoV-2-related and Covid-19 vaccine-induced thromboembolic events: A comparative review.

Since the start of the pandemic, thrombotic events have been a well-known and severe complication associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nevertheless, the initiation of vaccination programs brought another rare yet highly fatal thrombotic event, vaccine-induced immune thrombotic thrombocytopaenia, which has caused extensive debate regarding the safety of vaccines. This review defines the thromboembolic events following infection and vaccination, identifies their risk factors, describes their pathophysiology, and discusses their management, treatment, and prevention.

COVID-19 vaccine-related new-onset lichen planus.

Coronavirus disease 2019 (COVID-19) vaccines significantly impacted world health and well-being. However, various adverse events have been observed following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Cutaneous reactions have been prevalent following many vaccines, including COVID-19 vaccines. Here, we present a case of new-onset lichen planus in a patient who received the COVID-19 vaccine at the same time as being infected with SARS-CoV-2. A 52-year-old woman presented to the clinic with extensive pruritic skin lesions. The eruptions had appeared a week after her second dose of the Sinopharm COVID-19 vaccine. She mentioned a history of SARS-CoV-2 infection approximately 10 days following the first dose of her vaccine, causing a 1-month delay in getting the second dose. Her past medical history was not significant. On examination, erythematous and squamous papules were demonstrated predominantly on the extremities, including inguinal and axillary folds. Moreover, desquamation of the lips was visible, and buccal lesions were also found. After consultation with a dermatologist, a skin biopsy was indicated for the patient, but she refused to undergo the procedure. Therefore, considering the typical appearance of the eruptions, lichen planus was suspected, for which she was treated with oral antihistamines and topical corticosteroids.

Coronavirus disease 2019 infection in kidney transplant recipients: A clinical case series.

Kidney transplant recipients appear to be at increased risk for severe coronavirus disease 2019 (COVID-19) illness due to some factors such as comorbidities and chronic immunosuppression. Here, we report four cases of COVID-19 infection in kidney transplant recipients. The one case in this series with the high D-dimer levels and receiving tacrolimus had the worst outcome among reported patients. Other patients had better outcomes that probably due to the effect of immunosuppressive therapy in the prevention of COVID-19-induced cytokine storm. It was suggested that a high D-dimer level occurred in critical patients and likely prognostic and also, the immunosuppressive effect of some treatment regimens.

Pathophysiology and Management of Tongue Involvement in COVID-19 Patients

Evaluate the lingual manifestations of COVID-19, and provide a clinical guide in managing these symptoms. Electronic databases, such as PubMed/Medline, and Scopus were searched until November 1, 2020, and only randomized controlled trials, cross-sectional and cohort studies, as well as case reports and series, and review articles in English were considered. A total of 40 studies were included in this study. Lingual involvement has been extensively reported in patients with coronavirus disease 2019 (COVID-19). The most common features of lingual involvements were red or light red, yellow coating, and greasy coating tongue, though other complications, such as pale, purple, white coating, grayish-black coating, rough, tender, puffy, spotty, prickles, fissured, and tooth-marked tongue was also reported. Poor oral hygiene, opportunistic infections (OIs), medications, and hyper-inflammatory response to infection are the most common predisposing factors for the onset of oral lesions in patients with COVID-19. In conclusion, the current review described the lingual manifestations of COVID-19, and as oral complaints are relatively common in COVID-19 patients, an intraoral examination should be conducted in all suspected cases of SARS-CoV-2 infection.