Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Subacute Thyroiditis After Severe Acute Respiratory Syndrome Coronavirus 2 Vaxzevria Vaccination in a Patient With Thyroid Autoimmunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been challenging the scientific community to promptly treat the patients and mitigate its spreading. The rapid development of vaccination against SARS-CoV-2 is being highly effective, but it is still lacking knowledge about its side effects. Epidemiological studies point toward virus infection as causative agents of subacute thyroiditis. More than 20 cases of thyroiditis after SARS-CoV-2 have also been described. Here, we aim to broad the spectrum of SARS-CoV-2 vaccination thyroid-associated disorders with the description of a new case of subacute thyroiditis associated with thyroid autoimmunity. The temporal association with the inoculation of the vaccine and the absence of other plausible etiological agents makes it highly possible that this thyroiditis was caused by Vaxzevria vaccine. It remains to be established whether the presence of thyroid autoimmunity can facilitate this condition, as this is one of the few described cases associated with autoimmunity.

Delirium severity in critical patients with COVID-19 from an Infectious Disease Intensive Care Unit.

BACKGROUND: COVID-19 is mainly characterized by respiratory manifestations. Nevertheless, neurologic complications have been described, including delirium, which appears to be frequent, prolonged, and severe. METHODS: We conducted a retrospective analysis of demographic, clinical, and laboratory data of two cohorts: patients with COVID-19 admitted to the infectious disease intensive care unit (ID-ICU) and patients admitted to the ID-ICU with other respiratory infections in 2018-2019. Outcomes were defined as the presence, duration, and severity of delirium. Doses of antipsychotics used to control delirium were converted to equivalents and used as delirium severity. Logistics regression models were used to correlate COVID-19 with the outcomes. RESULTS: Ninety-nine patients with COVID-19 and 40 patients without COVID-19 were included. The mean age of the COVID-19 cohort was 63 years, with a male predominance. Delirium developed in 42%, with a median duration of 3 days and an equivalent dose of olanzapine use of 10 mg/day. In univariate analysis, COVID-19 was not associated with the development or different duration of delirium when compared with patients without COVID-19. There was an association between COVID-19 and severity of delirium in a binary logistic regression model controlled to confounding variables. CONCLUSION: COVID-19 is not associated with a higher prevalence or duration of delirium than in cohorts without COVID-19. However, it is associated with more severe forms of delirium.

SARS-CoV-2-related Multisystem Inflammatory Syndrome in Adults.

Adults infected with SARS-CoV-2 may develop a multisystem inflammatory syndrome (MIS-A) characterized by elevated inflammatory markers and multisystem organ involvement. We report the case of a patient who presented with fever and vomiting at hospital admission. He tested positive for SARS-CoV-2 infection and blood tests showed elevated inflammatory markers. The patient developed acute cardiac dysfunction and shock in less than 24 hours and the echocardiogram revealed an LVEF of 30%. He was discharged 3 weeks later fully recovered. MIS-A should be considered if a compatible syndrome is observed in patients with evidence of SARS-CoV-2 infection by PCR test or serology. LEARNING POINTS: Multisystem inflammatory syndrome should be considered in young adults presenting with shock and elevated inflammatory markers.Multisystem inflammatory syndrome may be highly responsive to parenteral steroids.

Complex regional pain syndrome after severe COVID-19 - A case report.

Neurological complications are frequently reported in an intensive care unit (ICU), as a manifestation of a critical systemic illness or of its treatment. On the specific setting of COVID-19 patients, peripheral nerve lesions can have a multiplicity of causes, such as post-infectious neuropathy, positioning-related neuropathy or iatrogeny. An unusual but potentially disabling complication of any peripheral nerve lesion is Complex Regional Pain Syndrome (CRPS). Although there have been no mechanistic studies assessing how SARS-CoV-2 might directly impact nociception, it is hypothesized that the systemic hyperinflammation seen in severe COVID-19 may contribute to peripheral and central neuronal sensitization, possibly increasing the risk of developing CRPS. This case report highlights the potential hazards and consequences of peripheral nerve injuries on an ICU setting in COVID-19 patients, as well as the importance of a multidisciplinary approach for an early diagnosis and treatment, which are directly related to a better prognosis.

Serological response to a single dose of a SARS-CoV-2 mRNA vaccine.

The delays in the production and delivery of COVID-19 vaccines and the growing number of fatal infections across the globe raised the question whether it would be more advantageous to vaccinate a larger group of individuals with one dose instead of a smaller one with two doses. Through a group of vaccinated healthcare workers, we describe the qualitative and quantitative serological response to a single dose of the BNT162b2 vaccine. We found that, before the second dose inoculation, 95.3 % (182/191) already had anti-SARS-CoV-2 IgG and, half of them, antibodies concentrations against RBD (the key target of neutralizing antibodies) that reached maximum values for the used evaluation immunoassay. In order to improve the execution of vaccination programs, further studies are needed to assess whether there are individuals for whom a single dose of mRNA vaccine or a delay in the inoculation of the second dose, produce a sufficient immune response. Additionally, follow-up studies will help in understanding post-vaccination immunity, how long it lasts and how it relates to infection and reinfection.

Impact of montelukast as add on treatment to the novel coronavirus pneumonia (COVID-19): protocol for an investigator-initiated open labeled randomized controlled pragmatic trial.

BACKGROUND: Montelukast, a safe drug widely use in asthmatic patients, may be an adjuvant in the treatment of Covid-19, either by improving lung injury and inflammation, or by acting as an anti-viral drug. We aim to assess the efficacy and safety of montelukast as add-on treatment in patients with Covid-19. METHODS: We propose a randomized, controlled, parallel, open-label trial involving 160 hospitalized adult patients with confirmed Covid-19. Patients will be randomly assigned in a 1:1 ratio to receive either montelukast 10 mg, once a day for 14 days, in addition to standard of care (SoC), or SoC alone. SoC will follow the best practice for treating these patients, according to updated recommendations. The primary outcome is time to recovery. Participants will be assessed using diary cards to capture data on treatment-related improvements in an 8-point ordinal scale. Secondary endpoints will include changes in respiratory and inflammatory parameters, and adverse events. This phase IV clinical trial will take place at the University Hospital of São João, Porto. EudraCT number: 2020-001747-21. RESULTS: This study intends to generate scientific evidence on efficacy and safety of montelukast as add-on treatment in Covid-19. The results will be essential to improve clinical outcomes which remains to be determined. CONCLUSION: Montelukast has been suggested as a potential drug with 2 main actions on Covid-19. The validation of montelukast as an adjuvant treatment may improve lung injury, inflammation, and symptoms leading to a better prognosis. The use of this drug may fulfil the existing gap on therapeutic options.

Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration.

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient's mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.