Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+ß7 integrin+ T cells and anti-SARS-CoV-2 IgA response.

Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor ß7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+ß7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.

Clinical Characteristics and Mortality-Associated Factors in COVID-19 Critical Patients in a Portuguese ICU.

INTRODUCTION: Severe COVID-19 is associated with serious complications and poor outcomes. Older age and underlying comorbidities are known risk factors for severe COVID-19, but a better understanding of baseline characteristics and outcomes of patients with severe COVID-19 is urgently needed. METHODS: This study was a retrospective case series of 227 consecutive patients with laboratory-confirmed COVID-19 admitted to the intensive care unit (ICU) at our institution between March 2020 and December 2021. Demographic and clinical data were collected. RESULTS: The median age of patients was 65 years, and 180 (79.3%) were male. Cardiovascular comorbidities were frequent and included hypertension (n=148; 65.2%), dyslipidemia (n=116; 51.1%), obesity (n=114; 50.2%), and diabetes mellitus (n=80; 35.2%). About 20% of the patients had the chronic respiratory disease, with sleep apnea being the most common. Immunosuppression was identified in 13% of the patients, with autoimmunity, post-transplantation, and neoplasms being the most represented causes. Most patients were admitted to the ICU at six to 15 days after symptom onset, corresponding to stages IIb (pulmonary involvement/hypoxia) and III (hyperinflammatory). All patients received systemic steroids, with an average treatment duration of 22 days. Several ventilatory support strategies were used; 80 patients were supported entirely noninvasively with high flow nasal oxygenation and noninvasive ventilation, while 164 patients were invasively ventilated. Most intubations (65%) occurred in the first 24 hours after admission, and the mean duration of mechanical ventilation was 14 days. The reintubation rate was 10%, occurring on average two to three days after planned extubation. Thirty-two tracheostomies were performed. Bacterial co-infection was treated in 75% of patients, and Aspergillus co-infection complicating COVID-19 pneumonia was diagnosed in eight patients. Median ICU and hospital stays were 15 and 25 days, respectively, and the 28-day mortality rate was 38%. Patients over 75 years experienced a higher mortality rate (56%). Increased age and multimorbidity, particularly comprising cardiovascular disease and associated risk factors, were significantly more common in patients who died within 28 days after ICU admission. CONCLUSIONS: A large proportion of critically ill COVID-19 patients required prolonged mechanical ventilation. ICU/hospital stay and mortality were particularly elevated in older patients and patients with cardiovascular risk factors. Considerable discrepancy existed between the proportion of patients with microbiological documentation of bacterial infections and those receiving antimicrobials. Improved methods for adequate microbiological diagnosis are needed and stewardship programs should be reinforced.

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.

Interleukin-6 Is a Biomarker for the Development of Fatal Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

Hyper-inflammatory responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major cause of disease severity and death. Predictive prognosis biomarkers to guide therapeutics are critically lacking. Several studies have indicated a "cytokine storm" with the release of interleukin-1 (IL-1), IL-6, and IL-8, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. Here, we proposed to assess the relationship between IL-6 and outcomes of patients with coronavirus disease 2019 (COVID-19). Our cohort consisted of 46 adult patients with PCR-proven SARS-CoV-2 infection admitted in a COVID-19 ward of the Hospital de Braga (HB) from April 7 to May 7, 2020, whose IL-6 levels were followed over time. We found that IL-6 levels were significantly different between the disease stages. Also, we found a significant negative correlation between IL-6 levels during stages IIb and III, peripheral oxygen saturation (SpO2), and partial pressure of oxygen in arterial blood (PaO2), showing that IL-6 correlates with respiratory failure. Compared to the inflammatory markers available in the clinic routine, we found a positive correlation between IL-6 and C-reactive protein (CRP). However, when we assessed the predictive value of these two markers, IL-6 behaves as a better predictor of disease progression. In a binary logistic regression, IL-6 level was the most significant predictor of the non-survivors group, when compared to age and CRP. Herein, we present IL-6 as a relevant tool for prognostic evaluation, mainly as a predictor of outcome.