Modulation of the immune response to SARS-CoV-2 vaccination by NSAIDs.

Evidence is scarce to guide the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate SARS-CoV-2 vaccine related adverse effects, given the possibility of blunting the desired immune response. In this pilot study, we deeply phenotyped a small number of volunteers who did or did not take NSAIDs concomitant with SARS-CoV-2 immunizations to seek initial information on the immune response. A SARS-CoV-2 vaccine specific RBD-IgG antibody response and efficacy in the evoked neutralization titers were evident irrespective of concomitant NSAID consumption. Given the sample size, only a large and consistent signal of immunomodulation would have been detectable, and this was not apparent. However, the information gathered may inform the design of a definitive clinical trial. Here, we report a series of divergent omics signals that invite additional hypotheses testing. Significance Statement A SARS-CoV-2 vaccine specific immune response was evident irrespective of concomitant NSAID consumption in a clinical pilot study of small sample size.

Early Multi-Target Treatment of Mild-to-Moderate COVID-19, Particularly in Terms of Non-Steroidal Anti-Inflammatory Drugs and Indomethacin

Recently, in Italy, a flowchart to be used by General Practitioners for the at-home treatment of patients with COVID-19, has been released. It states that early at-home treatment for SARS-CoV-2 infection is possible due to the availability of specific antiviral drugs to be used in at-risk patients, and that non-steroidal anti-inflammatory drugs (NSAIDs) have an important function in combating the virus. Therefore, the use of NSAIDs is not only rational but also effective in cases that cannot be treated using antivirals. These seemingly simple concepts have been applied in Italy since the beginning of the pandemic by doctors that belong to Italian groups created in order to help COVID-19 patients early at home, at a time of organizational difficulties within Italian health institutions and government. However, this approach was largely boycotted by both the Italian Ministry of Health and medical institutions, which mainly suggested the use of paracetamol as symptomatic, and a wait-and-watch approach for the first three days from the onset of symptoms. In this article, we analyze the rationale for the use of NSAIDs and, in particular, the multi-targeted approach including indomethacin in synergism with flavonoids and low-dose aspirin, as early at-home treatment of patients with COVID-19. Applying these simple concepts from the beginning could have reduced the high lethality of the disease during the first two years of the pandemic and prevented hospital overload. In perspective, it is still necessary to systematically address the comparison between different therapeutic approaches to this viral disease on an experimental basis. [ FROM AUTHOR] Copyright of BioMed is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Adverse drugs reactions to paracetamol and ibuprofen in children: a 5-year report from a pediatric poison control center in Italy.

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions. METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period. RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021. CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID-19: Might it also depend on their direct and/or indirect zinc chelating ability?

The present work argues for the involvement of the zinc chelating ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19.

Reactive arthritis occurring after COVID-19 infection: a narrative review.

PURPOSE: Reactive arthritis is acute aseptic arthritis occurring 1 to 4 weeks after a distant infection in a genetically predisposed individual. It may occur after COVID-19 infection. We summarize, in this article, the current findings of reactive arthritis following COVID-19 infection. METHODS: A literature search has been performed from December 2019 to December 2021. We included case reports of reactive arthritis occurring after COVID-19 infection. We collected demographic, clinical, and paraclinical data. RESULTS: A total of 22 articles were reviewed. There were 14 men and 11 women with a mean age of 44.96 + 17.47 years. Oligoarticular involvement of the lower limbs was the most frequent clinical presentation. The time between arthritis and COVID infection ranged from 6 to 48 days. The diagnosis was based on clinical and laboratory findings. The pharmacological management was based on non-steroidal anti-inflammatory drugs in 20 cases. Systemic or local steroid therapy was indicated in 13 patients. Sulfasalazine was indicated in two cases. Alleviation of symptoms and recovery were noted in 22 cases. The mean duration of the clinical resolution was 16 + 57 days. CONCLUSION: The diagnosis of reactive arthritis should be considered in patients with a new onset of arthritis following COVID-19 infection. Its mechanism is still unclear.

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID-19: Might it also depend on their direct and/or indirect zinc chelating ability?

The present work argues for the involvement of the zinc chelating ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19.

Egyptian perspectives on potential risk of paracetamol/acetaminophen-induced toxicities: Lessons learnt during COVID-19 pandemic.

Paracetamol/Acetaminophen was widely used as a first-line antipyretic and analgesic for COVID-19 patients without giving any attention to the potential risk of related toxicities. A survey was conducted on 176 Egyptians using an online survey portal to assess their knowledge, and attitude regarding potential risk of paracetamol toxicities and whether COVID-19 pandemic affected their practices regarding safe use of paracetamol. The self-administered questionnaire was developed by the researchers and was validated by expert opinions. A pilot testing of the questionnaire was done. Alpha Cronbach test used to assess the internal consistency reliability of the survey revealed good reliability. Overall percent-score revealed that only 24.4% of participants had good knowledge about paracetamol and its related potential toxicities. 62.5% of participants considered paracetamol safer than other medications of the same indications. 42.6% of participants could advise others to use paracetamol without prescription. According to the participants' responses, physicians were less concerned to give instructions about possibility of overdosage. Our results also revealed that participants' administration of paracetamol without physician prescription was more during COVID-19. Practice of paracetamol administration more than the allowed number of tablets/day was significantly more evident during the pandemic. We concluded that the unsupervised use of paracetamol is an alarming sign that should be addressed as this could lead to a high rate of accidental paracetamol toxicity. A lesson learnt from COVID-19 pandemic is the need to implement behavior change measures to mitigate the risk of accidental paracetamol toxicity.

Use of non-steroidal anti-inflammatory drugs during the COVID-19 pandemic. Resolution of the Expert Council of the Russian Society for the Prevention of Noncommunicable Diseases.

The spread and consequences of the coronavirus disease 2019 (COVID-19) pandemic are currently one of the most pressing public health challenges in the world. Despite the fact that experience accumulates in the treatment and monitoring of COVID-19 patients, certain aspects are still a clinical dilemma. In particular, this regarded the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during the pandemic, both as a symptomatic treatment of infection, and in patients with comorbidities requiring NSAID. A series of studies did not establish evidence of the risk of infection and complications from NSAID therapy in COVID-19. At the same time, the practitioner should take into account the risk of specific NSAID-associated complications, which also remain relevant during the COVID-19 pandemic. This resolution focuses on the evolution of ideas about NSAID use and safety in COVID-19, and also emphasizes the particular relevance of their use for a number of clinical situations. (English) [ FROM AUTHOR] Распространение и последствия пандемии новой коронавирусной инфекции COVID-19 (COronaVIrus Disease 2019) в настоящее время представляют одну из наиболее острых проблем системы здравоохранения в мире. Несмотря на то, что накапливается опыт лечения и наблюдения за пациентами с COVID-19, отдельные аспекты подходов к его управлению до сих пор составляют клиническую дилемму. Среди них, в частности, в течение определенного времени было использование нестероидных противовоспалительных препаратов (НПВП) в период пандемии как в качестве симптоматического лечения инфекции, так и у пациентов с сопутствующими заболеваниями, требующими назначения этого класса препаратов. Серия исследований позволила установить отсутствие данных, свидетельствующих о риске инфицирования и развития осложнений при использовании НПВП при COVID-19. Одновременно с этим практикующему врачу стоит принимать во внимание возможность развития класс-специфических осложнений, связанных с применением НПВП, которые остаются также актуальными в период пандемии COVID-19. Данная резолюция концентрирует внимание специалистов на эволюции представлений об использовании и безопасности НПВП при COVID-19, а также подчеркивает особую актуальность их применения для ряда клинических ситуаций. (Russian) [ FROM AUTHOR] Copyright of Cardiovascular Therapy & Prevention is the property of Silicea-Poligraf LLC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Acute PR3-ANCA vasculitis in an asymptomatic COVID-19 teenager.

We present the case of an acute onset ANCA positive vasculitis in an asymptomatic COVID-19 infected teenager, resulting in significant colonic damage. The patient was initially diagnosed with Henoch-Schönlein purpura and presented with worsening symptoms with significant necrosis of her perineum and rectum requiring surgical debridement and diverting colostomy. As a part of her work-up, she tested positive for COVID-19 total IgG/IgM antibodies and ANCA antibodies. This case complements previously reported cases of COVID-19 induced autoimmune disease in children but is novel in describing extensive intestinal disease as a result of an autoimmune vasculitis in a child.

Does immunosuppressive property of non-steroidal anti-inflammatory drugs (NSAIDs) reduce COVID-19 vaccine-induced systemic side effects?

To help stop the coronavirus disease 2019 (COVID-19) pandemic, vaccines are currently the most critical tool. However, the COVID-19 mRNA vaccines frequently cause systemic side effects shortly after the injection, such as fever, headache and generalized fatigue. In our survey, after receiving the second dose of the COVID-19 vaccine, 80% developed fever, 62% headache and 69% generalized fatigue. Among people who required antipyretics, the average durations of fever and headache were significantly shorter in those who took non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, loxoprofen and ibuprofen, than those who took acetaminophen. In our patch-clamp studies, NSAIDs effectively suppressed the delayed rectifier K+-channel (Kv1.3) currents in T-lymphocytes and thus exerted immunosuppressive effects. Because of this pharmacological property, the use of NSAIDs should be more effective in reducing the vaccine-induced systemic side effects that are caused primarily by the enhanced cellular immunity.

Significant decrease of facial cellulitis admissions during COVID-19 lockdown in France: A multicentric comparative study.

During the 2020 coronavirus pandemic, a lockdown was imposed in France during the first wave. An apparent decrease in incidence of cellulitis of odontogenic origin was noticed then. This study aimed to compare the incidence of cellulitis during this extraordinary period with the same period in 2018 and 2019, based on retrospective multicentric data. All maxillofacial surgery departments in French public hospitals were contacted. Responders were asked to include all patients admitted for the surgical drainage of a head and neck abscess of odontogenic origin during the first 2020 lockdown period, and in a similar time frame in 2018 and 2019 (control group), based on screening the French diagnostic and therapeutic classification of medical acts. We report a 44% significant nationwide decrease in the incidence of admissions for cellulitis. There were 187 patients in 2020 for 334 and 333 patients in 2018/2019 respectively. The reasons to explain this finding are hypothetical (organizational reasons leading to earlier management, patients' fear to seek for medical management, usual excess in surgical indications or concomitant decrease of non-steroidal anti-inflammatory drugs delivery). Whatever the explanation, it would be of great interest to find it out in order to improve the prevention of cellulitis.

Outcome of Conservative Therapy in Coronavirus disease-2019 Patients Presenting With Gastrointestinal Bleeding.

BACKGROUND/OBJECTIVE: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with Coronavirus disease -2019 (COVID-19) amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. METHODS: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22nd April to 22nd July 2020, were included. RESULTS: The mean age of patients was 45.8 ± 12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma (FFPs) and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. CONCLUSION: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.

COVID-19 in French patients with chronic inflammatory rheumatic diseases: Clinical features, risk factors and treatment adherence.

OBJECTIVE: To explore how patients with chronic inflammatory rheumatic diseases (CIRDs) coped with their disease during the COVID-19 pandemic and to identify possible predictive factors of SARS-CoV-2 infection in this population. METHODS: Patients followed in a single rheumatology department in France or registered on the Spondy+ platform, a secure e-health platform for spondyloarthritis patients, were invited to complete a questionnaire focused on their experiences around COVID19 symptoms, testing and medications access during the lockdown period. Descriptive statistics were used to report questionnaire's results. Factors associated with COVID-19 or with treatment discontinuation were assessed by logistic regression. RESULTS: We obtained 655 answers from the 2,081 contacted patients: 474 with spondyloarthritis, 129 with rheumatoid arthritis and 52 with psoriatic arthritis. The population was predominantly female (61.8%) with a mean age of 51.0±13.4 years. Incidence of COVID-19 was 6.9% (95%CI: 5.1-9.2%), including 12 confirmed and 33 highly suspicious cases. No death was observed and five patients needed to be hospitalized. Factors independently associated with an increased risk of infection were SARS-CoV-2 exposure, younger age and non-smoking. More than 30% of the patients suspended or decreased the dosage of one of their drugs during the lockdown period. This was followed in 63.4% of them by increased disease activity. Modifications were mostly motivated by fear of contagion (79.3%). CONCLUSION: We did not observe any increase of incidence or severity of COVID-19 in patients suffering of the 3 most common CIRDs. This survey also adds evidence of the safety of anti-rheumatic drugs use regarding COVID-19.

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.

Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association between prior NSAID use and time to mortality (adjusted HR (aHR) = 0.89, 95% CI 0.52-1.53, p = 0.67) or length of stay (aHR 0.89, 95% CI 0.59-1.35, p = 0.58). This study found no evidence that routine NSAID use was associated with higher COVID-19 mortality in hospitalised patients; therefore, patients should be advised to continue taking these medications until further evidence emerges. Our findings suggest that NSAID use might confer a modest benefit with regard to survival. However, as this finding was underpowered, further research is required.

COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use.

OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.

Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes.

Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10-5). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10-4), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10-4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.

COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting?

Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.