Anti-Inflammatory Therapy of Infections

Anti-inflammatory treatment of infections is challenging due to the heterogeneity of etiologic agents and complex immune interactions. Nevertheless, anti-inflammatory medications are commonly used in infections to reduce unpleasant symptoms and to modify host response. They may play a fundamental role in managing infection with over-inflammation by decreasing inflammatory organ damage, e.g., COVID-19. However, by its inherent inhibition of immune functions, they might also contribute to the development of serious bacterial infections. Moreover, reducing a patient's symptoms and signs may provide a false sense of security and delay diagnosing threatening infections. © 2022 Elsevier Inc. All rights reserved.

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.

Serological response after COVID-19 mRNA-1273 booster dose in immunocompromised patients, Taiwan, July to August 2021.

BACKGROUND: Whether immunocompromising conditions affect the immunogenicity of COVID-19 booster vaccination remains a concern, which impedes the vaccination campaign in people most vulnerable to COVID-19-associated morbidity and mortality. We aimed to evaluate the effect of immune dysfunction on immunogenicity of homologous and heterologous prime-boost COVID-19 vaccination. METHODS: Between July and August, 2021, 399 participants were randomized to receive ChAdOx1/ChAdOx1 8 weeks apart, ChAdOx1/mRNA-1273 8 weeks apart, ChAdOx1/mRNA-1273 4 weeks apart, and mRNA-1273/mRNA-1273 4 weeks apart. The anti-SARS-CoV-2 spike IgG antibody titers on the day before booster vaccination and 4 weeks after booster vaccination were compared between participants with and without immunocompromising conditions. RESULTS: Among ChAdOx1-primed participants, a trend of lower anti-SARS-CoV-2 spike IgG titers before booster vaccination were found in participants with autoimmune diseases (geometric means, 34.76 vs. 84.25 binding antibody units [BAU]/mL, P = 0.173), compared to those without. Participants receiving immunosuppressants and/or immunomodulators had significant lower anti-SARS-CoV-2 spike IgG titers before booster vaccination than those without (geometric means, 36.39 vs. 83.84 BAU/mL; P = 0.001). Among mRNA-1273-boosted participants, anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination were similar across all the strata. Participants with autoimmune diseases and receiving immunosuppressants and/or immunomodulators, had numerically lower anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination compared to those without (geometric means, 1474.34 vs. 1923.23 and 1590.61 vs. 1918.38 BAU/mL; P > 0.05). CONCLUSION: The immunogenicity of prime vaccination with ChAdOx1 decreased by immune dysfunction, but enhanced after receiving boost vaccination with mRNA-1273. Our study results support the efficacy of mRNA-1273 booster dose among immunocompromised hosts.

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.

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.

Antidepressant Effects of NSAIDs in Rodent Models of Depression-A Systematic Review.

In recent years much focus has been on neuroimmune mechanisms of depression. As a consequence, many preclinical and clinical trials have been performed examining potential antidepressant effects of several anti-inflammatory drugs. The results of such trials have been varied. With the current manuscript we wished to elucidate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on depressive-like behaviour in rodent models of depression by performing a systematic review of the available literature. We performed a systematic literature search in PubMed for rodent models of depression where NSAIDs were administered and a validated measure of depressive-like behaviour was applied. 858 studies were initially identified and screened using Covidence systematic review software. Of these 36 met the inclusion criteria and were included. The extracted articles contained data from both rat and mouse studies but primarily male animals were used. Several depression models were applied and 17 different NSAIDs were tested for antidepressant effects. Our results suggest that stress models are the best choice when examining antidepressant effects of NSAIDs. Furthermore, we found that rat models provide a more homogenous response than mouse models. Intriguingly, the use of female animals was only reported in three studies and these failed to find antidepressant effects of NSAIDs. This should be explored further. When comparing the different classes of NSAIDs, selective COX-2 inhibitors were shown to provide the most stable antidepressant effect compared to non-selective COX-inhibitors. Suggested mechanisms behind the antidepressant effects were attenuation of neuroinflammation, HPA-axis dysregulation and altered monoamine expression.

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.

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.