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.

Post-COVID-19 pulmonary fibrosis and its predictive factors: a prospective study

BackgroundWe aimed to prospectively assess the lung fibrotic-like changes, as well as to explore their predictive factors, in the patients who survived Coronavirus Disease 2019 (COVID-19) infection. In this prospective cross-sectional study, we recruited patients who had been treated for moderate or severe COVID-19 pneumonia as inpatients and discharged from Rohani hospital in Babol, northern Iran, during March 2020. The clinical severity of COVID-19 pneumonia was classified as per the definition by World Health Organization. We also calculated the CT severity score (CSS) for all patients at admission. Within the 3 months of follow-up, the next chest CT scan was performed. As the secondary outcome, the patients with fibrotic abnormalities in their second CT scan were followed up in the next 3 months.ResultsTotally, 173 COVID-19 patients were finally included in the study, of whom 57 (32.9%) were male and others were female. The mean age was 53.62 ± 13.67 years old. At 3-month CT follow-up, evidence of pulmonary fibrosis was observed in 90 patients (52.0%). Consolidation (odds ratio [OR] = 2.84), severe disease (OR 2.40), and a higher CSS (OR 1.10) at admission were associated with increased risk of fibrotic abnormalities found at 3-month CT follow-up. Of 62 patients who underwent chest CT scan again at 6 months of follow-up, 41 patients (66.1%) showed no considerable changes in the fibrotic findings, while the rest of 21 patients (33.9%) showed relatively diminished lung fibrosis.ConclusionPost-COVID-19 lung fibrosis was observed in about half of the survivors. Also, patients with severe COVID-19 pneumonia were at a higher risk of pulmonary fibrosis. Moreover, consolidation, as well as a higher CSS, in the initial chest CT scan, was associated with increased risk of post-COVID-19 lung fibrosis. In addition, some patients experienced diminished fibrotic abnormalities in their chest CT on 6-month follow-up, while some others did not.

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.

Fulminant hepatitis following COVID-19 vaccination: A case report.

The common side effects of COVID-19 vaccination were mostly self-restricted local reactions that quickly resolved. Nevertheless, rare autoimmune hepatitis cases have been reported in some vaccinated with mRNA COVID-19 vaccines. This article presents a young man who developed fulminant hepatitis a few days after vaccination with the first dose of the AstraZeneca COVID-19 vaccine. A 35-year-old man was admitted to our hospital with generalized weakness, abdominal pain, and jaundice. He received the first dose of the AstraZeneca COVID-19 vaccine 8 days earlier. He was admitted to the hospital with a chief complaint of abdominal pain. On admission and because of his high D-dimers, low platelet count, and low Fibrinogen level, vaccine-induced immune thrombosis thrombocytopenia was suspected, which was ruled out later. Then, after a surge in his liver function tests, decreasing platelet, and abnormal clotting tests, fulminant hepatitis was considered for this patient. Several bacterial, viral, and autoimmune etiologies were then suspected, with all ruled out. Thus, fulminant hepatitis secondary to his AstraZeneca COVID-19 vaccine was confirmed. Unfortunately, he died 3 days later of disseminated intravascular coagulopathy, after which a liver necropsy was performed, indicating drug/toxin-induced hepatitis.

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.

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.

Optimal cut points of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) in patients with COVID-19.

BACKGROUND: COVID19 patients may suffer from multiple cardiovascular complications. Recently, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) was a potentially independent risk factor for COVID-19 in-hospital death. The present study aimed to find new optimal cut points for NT-proBNP across censored survival failure time outcomes in hospitalized COVID-19 patients. RESULTS: This cohort study was conducted on 272 patients with COVID-19 whose initial records were recorded from March 2020 to July 2020. Demographic characteristics, clinical examinations, and laboratory measurements were collected at the beginning of the admission registered in the patient record system located in the hospital. We used the maximally selected rank statistics to determine the optimal cut points for NT-proBNP (the most significant split based on the standardized log-rank test). Survival time was defined as the days from hospital admission to discharge day. In this cohort study, two optimal cut points for NT-proBNP were 331 (pg/mL) and 11,126 (pg/mL) based on a survival model. The adjusted HR of NT-proBNP for in-hospital death was 3.41 (95% CI: 1.22-9.51, P = 0.02) for medium against low category, and 3.84 (95% CI: 1.30-11.57, P = 0.01) for high in comparison with low group. CONCLUSIONS: We reported a dramatically increased concentration of NT-proBNP among COVID-19 patients without heart failure in both severe and non-severe cases. Moreover, our study showed that a high level of NT-proBNP was highly associated with the prolonged survival time of patients with COVID-19. NT-proBNP is a strong prognostic indicator of in-hospital death in the second week of admission.

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.