Immunopathology of SARS-CoV-2 virus infection

Introduction: the daily increase in cases and deaths, the economic losses in the millions suffered by affected nations and the consequent strain on the human resources involved in reversing this situation have made the COVID-19 pandemic an unprecedented international challenge. Background: to describe the orchestrated immune response following SARS-CoV-2 infection. Methods: an up-to-date bibliometric study was conducted on the type of articles stated in the objective, using a total of 30 bibliographies. Documentary review and analysis-synthesis methods were used to prepare the final report. Resources available on the Infomed network were used to select the information, specifically: PubMed and SciELO, through the databases: Medline, Search Premier and Scopus. Development: the core elements in the immunopathology of COVID-19 involve innate immunity, with the sustained increase of pro-inflammatory interleukins associated with failures in the interferon system, which can trigger a potentially fatal cytokine storm. In terms of elements linked to adaptive immunity, there is evidence of marked lymphopenia which, depending on the degree, may indicate the severity of the disease. Conclusions: understanding the orchestrated immune response following SARS-CoV-2 infection and its temporal sequence allows us to choose timely and effective therapies, specifically when selecting anti-inflammatory drugs and the time of their application, as it is difficult to determine when they will be clearly beneficial, that they do not impair the response and that it is not too late, given the irreversibility of the process.

Exacerbation of psoriasis vulgaris induced by vaccine COVID-19 in HIV patient: a case report

Background: Psoriasis is a chronic and inflammatory skin disease. Many triggering factors can cause exacerbation of psoriasis, such as infection, trauma, and drugs. Several vaccines are known to cause new lesions or exacerbation of psoriasis, including Bacillus Calmette-Guerin (BCG), influenza, tetanus-diphtheria, and pneumococcal polysaccharide. In the COVID-19 pandemic, the COVID-19 vaccine is known to cause the appearance of new lesions or exacerbation of psoriasis. Case presentation: A woman, 31 years old, came to the clinic with itchy reddish patches with white scales on her face, chest, stomach, back, arms, and both legs, and increased since 2 weeks ago. Previously, the patient got the first COVID-19 vaccine (Sinovac), and three days later, red patches appeared with white scales on the chest, stomach, and back. The patient had been diagnosed with psoriasis 3 years ago. Dermatology examination showed reddish patches with white scales on the face, chest, stomach, back, arms, and both legs. Auspitz sign and Kaarvetsvlek phenomen were positive. PASI score was 9,2. Dermoscopy examination showed red dot distribution on light pink background and white scales. She was treated with desoximetasone cream 0,05% twice a day and cetirizine tablet 10 mg once a day. After 2 months of therapy, reddish patches were decreased, and the PASI score was 6,9. Conclusion: COVID-19 vaccine can cause exacerbations in psoriasis patients, but this vaccine can still be given to psoriasis patients. It is based on the documented efficacy of the COVID-19 vaccine in the prevention of severe COVID-19 infection and fatality. Psoriasis patients should be consulted before getting vaccinated for COVID-19, and prompt clinical visits should be available if exacerbation develops.

Progress in the treatment of coronavirus pneumonia

Coronavirus pneumonia is caused by eoronavirus infection. Severe acute respiratory syndrome (SARS) in 2003, Middle east respiratory syndrome (MERS) in 2012, and coronavirus disease 2019 (COV1D-19) in 2019 were all caused by coronavirus. The prevalence of these diseases has caused great disaster to people all over the world. However, there is no specific drug for the treatment of coronavirus pneumonia. In View of the current worldwide epidemic situation of covid-19, it is particularly urgent to develop effective antiviral drugs. This article reviews the progress in the treatment of new coronavirus pneumonia, hoping to provide help for the prevention and control of the disease.

A case report of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 in Maha Sarakham, Thailand

We report a case of a 19-year-old female with multisystemic inflammatory syndrome that was associated with the novel coronavirs disease 2019 (COVID-19), which manifested as serious illness that occurred four weeks after COVID-19 infection. Her clinical manifestations involved multiple organ systems including high-grade fever with shock syndrome, pulmonary edema, myopericarditis with pericardial effusion, hepatitis, generalized maculopapular rash, and several elevated inflammatory markers. She was treated with human immunoglobulin, methylprednisolone, acetylsalicylic acid, enoxaparin, and empirical antibiotics. She required a 2-week hospitalization and was discharged after improvement of clinical symptoms and normalization of inflammatory markers. A day prior to discharge, an echocardiography was done and it showed normal ventricular function and no coronary aneurysmal dilation.

Causal inference during a pandemic: evidence on the effectiveness of nebulized ibuprofen as an unproven treatment for COVID-19 in Argentina

Many medical decisions during the pandemic were made without the support of causal evidence obtained in clinical trials. We study the case of nebulized ibuprofen (NaIHS), a drug that was extensively used on COVID-19 patients in Argentina amidst wild claims about its effectiveness and without regulatory approval. We study data on 5,146 patients hospitalized in 11 health centers spread over 4 provinces, of which a total of 1,019 (19.8%) received the treatment. We find a large, negative and statistically significant correlation between NaIHS treatment and mortality using inverse probability weighting estimators. We consider several threats to identification, including the selection of "low" risks into NaIHS, spillovers affecting patients in the control group, and differences in the quality of care in centers that use NaIHS. While the negative correlation appears to be, broadly, robust, our results are best interpreted as emphasizing the benefits of running a randomized controlled trial and the challenges of incorporating information produced in other, less rigorous circumstances.

Clinical value of diammonium glycyrrhizinate in treatment of COVID-19

To determine the clinical value of diammonium glycyrrhizinate (DG) in treatment of patients with novel coronavirus pneumonia (NCP). According to the random-number method, 104 NCP patients were divided equally into control group and observation group in our hospital. In the control group, patients were treated according to the Pneumonia diagnosis and treatment scheme for new coronavirus infection (trial version 5). In the observation group, patients were administered DG enteric capsules (150 mg, t.d.s.). All patients were treated continuously for 2 weeks. The clinical effects in both groups were observed. Levels of inflammation indicators [C-reactive protein (CRP), interleukin (IL) -4, tumor necrosis factor (TNF) -a] and immune-function indicators [cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+] were compared between the two groups. Adverse reactions were documented. The prevalence of cure [19.23% (10/52) vs. 7.69% (4/ 52)], significant efficacy [28.85% (15/52) vs. 17.31% (9/52)] and total efficacy [61.54% (32/52) vs. 40.38% (20/52)] of the observation group was significantly higher than that of the control group (P < 0.05 for all). After treatment, the serum levels of CRP [(1.90 +or- 085) vs. (3.26 +or- 1.63) mg/L], IL-4 [(21.35 +or- 8.90) vs. (26.24 +or- 9.16) pg/mL], and TNF-a [(4.85 +or- 2.15) vs. (7.97 +or- 3.36) pg/mL] of the observation group were significantly lower than those of the control group (P < 0.05 for all). The levels of CD3+ [(6630 +or- 8.83)% vs. (54.19 +or- 7.79)%], CD4+ [(39.42 +or- 4.72)% vs, (33.18 +or- 4.10)%], CD8+ [(28.14 +or- 4.22)% vs. (23.39 +or- 3.88)%], and CD4+/CD8+ [(1.62+or- 043) vs. (1.21 +or- 0.29)] of the observation group were significantly higher than those of the control group (P < 0.05 for all). The prevalence of adverse reactions [15.38% (8/52) vs. 28.85% (15/52)] of the observation group was significantly lower than that of the control group (P < 0.05). DG has a significant clinical effect and a good safety profile for NCP treatment.

Acute mesenteric ischemia as a complication of COVID-19 infection: a case report and review of the literature

Background: Coronavirus disease 2019 (COVID-19) is a major health problem worldwide. Vascular thrombosis is increasingly observed in COVID-19 patients. This complication seems to be due to coagulopathy and endothelial damage. In this paper, we report a COVID-19 patient with superior mesenteric artery thrombosis and review of 27 COVID-19 cases with acute mesenteric ischemia (AMI). Case presentation: A 59-years old man with confirmed COVID-19 readmitted to the hospital due to abdominal pain and diarrhea two days after discharge from the emergency department. He was diagnosed with acute mesenteric ischemia by abdominal CT scan with contrast. The patient underwent emergency laparotomy and the ischemic gangrenous bowel was resected. Unfortunately, the patient succumbed one month after the operation.

Comparison of public health measures taken during Spanish flu and COVID-19 pandemics: a narrative review

The similarity of the consequences of COVID-19 reminded us of the destruction caused by the Spanish flu over a century ago and led us to find similarities in the way the two pandemics were handled. PRISMA Guideline was followed for a systematic search to identify eligible published articles. Information about the public health measures adopted during both the pandemics was taken from literature. It was found that there are parallels between the two pandemics in terms of general unpreparedness, attitudes of the community and government, and various policy issues. All the measures implemented in 2020 were the same as those implemented in 1918-1919, with the same trend, uncertainty, early relaxing, and rapid reversals. Even from a scientific standpoint, all the elements were already known. All the issues such as social isolation, intra-family spread, personal protective equipment, medicine types (quinine, aspirin, anti-inflammatories, etc.), immunization requirements, and so on had already been addressed. No doubt, we do have technology today at our disposal for managing the spread of the disease and even spread awareness among people much easily. We also have taken many steps forward in the world of globalization, which make the progression and spread of the pandemic very fast as well. Both factors tend to counter each other and hence make timely public health intervention as important (if not more) today as it was yesterday. When possible, approaches and goals should be found on scientific facts and include ethical input. Finally, we must take careful notice of past local and national lessons to avoid repeating the mistakes done in the past. The development of a strategy ahead of time that includes all levels of government health infrastructure and outlines clear lines of duties and functions is critical. The main objective of this article was to compare the public health measures undertaken during the pandemic of Spanish Flu and the pandemic of COVID-19, and assess the similarities and differences in the public health measures taken during these pandemics. The correlation of the public health measures and the outcomes was assessed and the implication of this article was to be pandemic-ready in the future.

COVID-19: a review of treatment strategies and candidate vaccines

COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the acute respiratory syndrome, acute inflammatory response of the respiratory system, vascular injury, microangiopathy, angiogenesis, and widespread thrombosis. Four stages of COVID-19 have been determined;the first stage starts with an upper respiratory tract infection, the second stage starts by the onset of shortness of breath and pneumonia, the third stage starts by worsening of clinical symptoms followed by hyperinflammation, and the fourth stage is death or recovery of the patient. There is currently no successful treatment specifically for SARS-CoV-2 infection. Based on the pathological features and different clinical stages of COVID-19, especially in patients with moderate to severe COVID-19, the drug groups used includeed antiviral agents, anti-inflammatory drugs/anti-trauma drugs, and heparin with Low molecular weight, plasma, and hyperimmune immunoglobulin. During the emergency of the COVID-19 outbreak, clinical researchers are using a variety of possible therapies to test them. It seems that the precision medicine approach can answer the COVID-19 treatment questions. Therefore, the way to precision medicine in COVID-19 needs an extremely rapid pace. The aim of the present study was to discuss the most up-to-date effective drugs and vaccines against SARS-CoV-2 infection.

Non-steroidal anti-inflammatory drugs amid COVID-19 pandemic: an ally or an enemy?

As the current global pandemic of the novel coronavirus diseases 2019 (COVID-19) continues to rage, the scientific and medical worlds are working to establish an effective therapy against the illness. Recently questions regarding non-steroidal anti-inflammatory drugs (NSAIDs) as a potential therapeutic option for COVID-19 have surfaced. While some studies hint towards the possible benefit of NSAIDs against SARS-CoV-2 infection, the current body of evidence also sheds light on the potential risk of using NSAIDs in COVID-19 patients. Thus, the available literature does not provide conclusive evidence for or against the use of NSAIDs for treating COVID-19 patients. Given the limited data available, we suggest cautionary approaches for the public to avoid possible harm until further evidence emerges. NSAIDs should not be used as the first-line agents for COVID-19 unlessunder medical supervision. Moreover, patients with chronic inflammatory conditions should continue the NSAIDs as per their regular prescriptions.

Paracetamol (acetaminophen) toxicisis in companion animals

Paracetamol is an analgesic and antipyretic with less anti-inflammatory properties than non-steroidal anti-inflammatory drugs, indicated in the symptomatic treatment of mild to moderate pain and the symptomatic treatment of fever. It is found in a variety of over-the-counter analgesic combinations (tablets, suppositories, children's syrups). Poisoning is due to use by pet (dogs, kats) owners without veterinary advice. The risk is high at present due to movement restrictions on people imposed by the Covid pandemic. Cats are the most susceptible. Poisoning is manifested by methaemoglobinaemia, haemolytic anaemia or toxic hepatosis.

Acute myopericarditis in a pediatric patient after first dose of Pfizer BioNTech COVID-19 vaccination: first case report in the Kingdom of Bahrain

Coronavirus disease 201 9 (COVID-1 9) vaccination for children over 12 years of age began on May 2021 in the kingdom of Bahrain. Very limited data is available regarding the adverse events related to COVID-19 vaccination in children. This is a case report of a 12-year-old previously healthy boy with acute myopericarditis who presented on day 5 after the first dose of Pfizer COVID-19 vaccination. Other causes of acute myopericarditis were ruled out. He was treated with non-steroidal anti-inflammatory drugs and recovered fully. This case of vaccine-induced myocarditis was reported to the national task force of Bahrain for combating COVID -19.

Efficacy of Sofosbuvir and Daclatasvir on the prognosis of kidney transplantation recipients with SARS-CoV-2 infection;a single-center study in Shariati Hospital

Introduction. The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-COV-2), was reported in Wuhan, China, in early December 2019 and spread rapidly worldwide. In the COVID-19 era, Kidney transplantation recipients (KTRs) are at high risk due to using immunosuppressive drugs. Therefore, finding an efficient treatment for the management of COVID-19 in KTR patients is crucial due to its poor prognosis. Despite the use of various antiviral and anti-inflammatory drugs, there is yet no definitive cure for Covid-19. Repurposing existing pharmaceuticals is a way to find an immediate medication. Thus, we assessed the antiviral treatment efficacy of Sofosbuvir combined with Daclatasvir on KTRs with SARS-COV-2 infection. Methods. We conducted a single-center retrospective cross-sectional study of all adult kidney transplant recipients with COVID-19, admitted to Shariati Hospital, Tehran, Iran, from October to December 2020. All the patients received a once-daily combination pill of SOF and DAC at a dose of 400/60 mg for 10 days. The study protocol was approved by the Ethical Committee of the Tehran University of Medical Sciences under ID: IR. TUMS. DDRI. REC.1399.028. Statistical analysis was performed using IBM SPSS version 26.0. A P value less than 0.05 was considered statistically significant for all tests. Results. From October to December 2020, 12 adult KTR patients were recruited;four patients (33.3%) died and eight patients survived (66.7%). The dead patients were older than those who survived. However, it was not statistical significance (53.67 .. 3.786 vs. 47.63 .. 11.868, P = 0.422). Acute kidney injury (AKI) due to COVID-19 infection was seen in 11 patients of the study population (91.7%) and all four dead KTRs. Also, three patients underwent dialysis, which two died (50%). The most common comorbidities were hypertension (6 patients, 50%) and diabetes mellitus (4 patients, 33.3%), while no significant correlation was seen between comorbidities and mortality (P > 0.05). About the immunosuppressive drugs, of four dead patients, three (75%) used Mycophenolate, and all of them used Prednisolone. The laboratory results showed that the mean level of each parameter WBC, INR, CRP, Ferritin, D-Dimer on the last day of hospital stay was significantly different between two groups of survived and dead patients at a 95% confidence level (P < 0.05). Conclusion. Sofosbuvir combined with Daclatasvir for treatment of KTRs with SARS-COV-2 infection showed efficacy by reducing the mortality rate. Also, the medication was safe. Patients tolerated it well, and no serious adverse effects were observed. Larger studies are needed to validate these results.

Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection. (Special issue: Drugs and COVID-19.)

Non-steroidal anti-inflammatory drugs (NSAIDs) have an optional prescription status that has resulted in frequent use, in particular for the symptomatic treatment of fever and non-rheumatic pain. In 2019, a multi-source analysis of complementary pharmacological data showed that using NSAIDs in these indications (potentially indicative of an underlying infection) increases the risk of a severe bacterial complication, in particular in the case of lung infections. First, the clinical observations of the French Pharmacovigilance Network showed that severe bacterial infections can occur even after a short NSAID treatment, and even if the NSAID is associated with an antibiotic. Second, pharmacoepidemiological studies, some of which minimized the protopathic bias, all converged and confirmed the risk. Third, experimental in vitro and in vivo animal studies suggest several biological mechanisms, which strengthens a causal link beyond the well-known risk of delaying the care of the infection (immunomodulatory effects, effects on S. pyogenes infections, and reduced antibiotics efficacy). Therefore, in case of infection, symptomatic treatment with NSAIDs for non-severe symptoms (fever, pain, or myalgia) is not to be recommended, given a range of clinical and scientific arguments supporting an increased risk of severe bacterial complication. Besides, the existence of a safer drug alternative, with paracetamol at recommended doses, makes this recommendation of precaution and common sense even more legitimate. In 2020, such recommendation is more topical than ever with the emergence of COVID-19, especially since it results in fever, headaches, muscular pain, and cough, and is further complicated with pneumopathy, and given experimental data suggesting a link between ibuprofen and the level of expression of angiotensin-converting enzyme 2.

Current pharmacological treatments for COVID-19: What's next?

Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.