Expression profile of HERVs and inflammatory mediators detected in nasal mucosa as a predictive biomarker of COVID-19 severity.

Introduction: Our research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome. Methods: Residuals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR. Results: The results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1ß, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-ß, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1ß, IL-6, IFN-α, and IFN-ß reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation. Discussion: Overall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

Effects of SARS-CoV-2 on Pulmonary Function and Muscle Strength Testing in Military Subjects According to the Period of Infection: Cross-Sectional Study.

BACKGROUND: Pulmonary function can be impaired as a long-term consequence of SARS-CoV-2 infection. The aim of this study was to evaluate the effect of SARS-CoV-2 infection on pulmonary function, exercise tolerance, and muscle strength in healthy middle-aged military outpatients according during the period of infection. METHODS: A cross-sectional study was carried out from March 2020 to November 2022 at the Military Hospital "Celio" (Rome, Italy). If someone had a diagnosis of SARS-CoV-2 infection certified by molecular nasal swab and if they performed pulmonary function tests, diffusion of carbon monoxide (DL'co), a six Minute Walk Test (6MWT), a Handgrip (HG) Test, and a One Minute Sit to Stand Test (1'STST). The included subjects were divided into two groups, A and B, according to the period of infection: A) from March 2020 to August 2021 and B) from September 2021 to October 2022. RESULTS: One hundred fifty-three subjects were included in the study: 79 in Group A and 74 in Group B. Although the values were within the normal range, Group A had smaller FVC, FEV1, and DL'co compared to Group B. Group A also walked a shorter distance at the 6MWT and performed fewer repetitions in the 1'STS test compared to Group B. In both groups, the DL'co (%predicted) correlated with the 6MWT distance (R2 = 0.107, p < 0.001), the number of repetitions of the 1'STST (R2 = 0.086, p = 0.001), and the strength at the HG test (R2 = 0.08, p < 0.001). CONCLUSIONS: This study shows that the SARS-CoV-2 infection in healthy middle-aged military outpatients was more severe in the first waves than in the later ones and that, in healthy and physically fit individuals, even a marginal reduction in resting respiratory test values can have a major impact on exercise tolerance and muscles strength. Moreover, it shows that those infected more recently had symptoms related to the upper respiratory tract infection compared to those of the first waves.

Hypocalcemia is associated with adverse outcomes in patients hospitalized with COVID-19.

PURPOSE: Calcium ions are involved in the regulation of several cellular processes and may also influence viral replication. Hypocalcemia has been frequently reported during infectious diseases and in critically ill patients, including also COVID-19 patients, significantly related with the pro-inflammatory state and mortality. The aim of this study is to investigate the prevalence of hypocalcemia at admission in patients hospitalized for COVID-19 (Coronavirus disease 2019) and to evaluate association of hypocalcemia with in-hospital COVID-19 outcomes. METHODS: Retrospective analysis on 118 consecutive patients, hospitalized for COVID-19 between March and May 2020. Clinical characteristics, inflammation markers, biochemical routine and mineral metabolism parameters at admission were collected. Hypocalcemia was defined as total serum calcium <2.2 mmol/L. Population was stratified by tertiles of total serum calcium. Primary outcome was the composite of in-hospital death or admission to intensive care unit (ICU). Secondary outcomes included in-hospital death, admission to ICU and need for non-invasive ventilation as separate events. Associations were tested by logistic regression and Cox-regression analysis with survival curves. RESULTS: Overall prevalence of hypocalcemia was 76.6%, with just 6.7% of patients reporting levels of 25-(OH)-vitamin D > 30 ng/ml. Total serum calcium was inversely related with selected inflammatory biomarkers (p < 0.05) and poorer outcome of COVID-19 during hospitalization. Lower tertile of total calcium (≤2.02 mmol/L) had increased risk of in-hospital mortality (HR 2.77; 1.28-6.03, p = 0.01) compared with other groups. CONCLUSION: Total serum calcium detected on admission is inversely related with proinflammatory biomarkers of severe COVID-19 and is useful to better define risk stratification for adverse in-hospital outcome.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Expert guidance on the management and challenges of long-COVID syndrome: a systematic review.

INTRODUCTION: Long-COVID is a condition characterized by the permanence of symptoms beyond 4 weeks after an initial infection. It affects 1 out of 5 people and is loosely related to the severity of acute infection and pathological mechanisms, which are yet to be understood. AREAS COVERED: This article looks at currently available and under-studied therapies for long-COVID syndrome. It particularly gives focus to ongoing trials and reviews the underlying mechanisms. A comprehensive literature search was performed on PubMed and clincaltrial.gov of clinical trials concerning the management of long-COVID syndrome. EXPERT OPINION: 'Long-COVID' syndrome is a new emergency characterized by several symptoms such as fatigue, dyspnea, cognitive and attention disorders, sleep disorders, post-traumatic stress disorder, muscle pain, and concentration problems. Despite the many guidelines available to date, there are no established treatments of long-COVID. Pharmacological research is studying known drugs that act on the reduction or modulation of systemic inflammation, or innovative drugs used in similar pathologies. Rehabilitation now seems to be the safest treatment to offer, whereas we will have to wait for the pharmacological research trials in progress as well as plan new trials based on a better understanding of the pathogenic mechanisms.

Effects of SARS-CoV-2 Infection on Pulmonary Function Tests and Exercise Tolerance.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause long-term pulmonary sequelae. OBJECTS: The aim of this study was to evaluate the consequences of the SARS-CoV-2 infection on pulmonary function and on the 6-min walk test related to the severity of the disease. METHODS: A cross-sectional study was conducted at the "Policlinico Tor Vergata" Academic Hospital (Rome, Italy), including 75 patients evaluated in post-COVID clinics at the Respiratory Units between November 2020 and September 2021. Complete pulmonary function tests, 6-min walk tests and persistence of symptoms were performed. RESULTS: Of the 75 subjects, 23 had mild, 16 moderate, 26 severe and 10 very severe COVID-19, classified according to WHO. Very severe patients had a lower FVC (100 ± 10%pr) compared to the other groups (116 ± 16%pr, 116 ± 13%pr, 122 ± 20%pr from mild to severe; p < 0.05) and a lower TLC (94 ± 13%pr) compared to the others (102 ± 10%pr, 108 ± 15%pr, 108 ± 12%pr from mild to severe; p < 0.05). DLco and DLco/VA were similar among groups. At the 6MWT, distance, rest and nadir SpO2 were similar among groups, but all groups presented a significant decrease in SpO2 from rest to nadir (Rest SpO2: 97.0 ± 1.0% vs. Nadir SpO2: 93.6 ± 2.7%, p < 0.01). A positive correlation was found between desaturation and delta SpO2 (rest-nadir) (R: 0.29, p < 0.05) and the Distance Desaturation Product (R: 0.39, p < 0.01). CONCLUSIONS: These results showed that, although the PFTs are within the normal range, there is still a mild restrictive spirometric pattern after six months in very severe subjects. Moreover, the only persistent pathological sequalae of SARS-CoV-2 infection were a mild desaturation at 6MWT, despite the severity of the infection.

First Case of a COVID-19 Patient Infected by Delta AY.4 with a Rare Deletion Leading to a N Gene Target Failure by a Specific Real Time PCR Assay: Novel Omicron VOC Might Be Doing Similar Scenario?

Herein, we report a case of an Italian male infected by Delta sublineage AY.4 harboring an atypical deletion, leading to a N gene target failure (NGTF) by a commercial molecular assay for SARS-CoV-2 diagnosis (AllplexTM SARS-CoV-2 Assay, Seegene). A 59-year-old unvaccinated patient was hospitalized for pulmonary embolism, with first negative results obtained by both molecular and antigen tests. After several days of viral negativity, he presented positive results for E and RdRP/S genes, but negative in N gene. Negativity in N gene was repeatedly confirmed in the following days. Suspecting an infection by the Omicron variant, SARS-CoV-2 genome sequencing was rapidly performed from nasopharyngeal swab by MiSeq and revealed the presence of the Delta sublineage AY.4 variant with an atypical deletion of six nucleotides, leading to G214-G215 deletion in the Nucleocapsid, thus responsible for NGTF. The analysis of GISAID sequences (N = 2,618,373 12 January 2022) showed that G214-G215 deletion is rarely occurring in most circulating Delta lineages and sublineages in the globe and Europe, with an overall prevalence never exceeding 0.2%. Hence, this study highlights the importance to perform SARS-CoV-2 sequencing and to characterize novel mutations/deletions that could jeopardize the proper interpretation of molecular diagnostic tests. Based on these assumptions, the role of deletions in the recently identified Omicron variant deserves further investigation.

Use of face masks and allergic nasal symptoms: Why not mention pollen count and air pollution data?

The scientific quantification of symptoms in pollen-related allergic rhinitis cannot be separated from the aerobiological data of the geographical area in which the study was carried out.

Dexamethasone in Patients Hospitalized with COVID-19: Whether, When and to Whom.

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9-65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0-13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1-79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1-50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9-20.6) in subjects <70 years, 27.0 (95%CI 18.5-49.8) in men, and 16.2 (95%CI 13.2-20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support.

Use of Thiols in the Treatment of COVID-19: Current Evidence.

There is a possible role for oxidative stress, a state characterized by an altered balance between the production of free radicals or reactive oxygen species (ROS) and antioxidant defences, in coronavirus disease 2019 (COVID-19), the genesis of which is quite complex. Excessive oxidative stress could be responsible for the alveolar damage, thrombosis, and red blood cell dysregulation observed in COVID-19. Apparently, deficiency of glutathione (GSH), a low-molecular-weight thiol that is the most important non-enzymatic antioxidant molecule and has the potential to keep the cytokine storm in check, is a plausible explanation for the severe manifestations and death in COVID-19 patients. Thiol drugs, which are considered mucolytic, also possess potent antioxidant and anti-inflammatory properties. They exhibit antibacterial activity against a variety of medically important bacteria and may be an effective strategy against influenza virus infection. The importance of oxidative stress during COVID-19 and the various pharmacological characteristics of thiol-based drugs suggest a possible role of thiols in the treatment of COVID-19. Oral and intravenous GSH, as well as GSH precursors such as N-acetylcysteine (NAC), or drugs containing the thiol moiety (erdosteine) may represent a novel therapeutic approach to block NF-kB and address the cytokine storm syndrome and respiratory distress observed in COVID-19 pneumonia patients.

Controversy surrounding the Sputnik V vaccine.

The Sputnik V COVID-19 vaccine is a member of the so-called vector vaccines and uses two different vectors (Ad26 priming and Ad5 boost) to reduce the risk of a reduction in the effectiveness of the vaccination. Real life data indicate an efficacy of the vaccine above 97%. Low cost and no need for ultra-cold storage temperature temperatures are other pluses of the Sputnik V vaccine. However, there are also several important shortcomings that must be considered such as the possible reduction of its immunogenicity in the presence of very high Ad5 neutralizing antibody titres and the decrease with age of the antibody titres neutralizing the virus. Furthermore, there is emerging documentation that Sputnik V has a reduced neutralizing capacity against the Beta variant and all variants with the spike protein carrying the E484K substitution. Nevertheless, due to its characteristics, Sputnik V could be another useful means of satisfying the need for mass vaccination. However, it is imperative to document the efficacy and safety of the Sputnik V vaccine in individuals with high pre-existing anti-Ad26 and Ad5-neutralizing antibody titres and in those under the age of 18 or older than 60 years and be certain that Sputnik V does not cause the rare development of immune thrombotic thrombocytopenia. It is hoped that the now widespread use of this vaccine will generate a large pragmatic real-world study with data accessible to anyone interested in verifying them.

Atherogenic Dyslipidemia on Admission Is Associated With Poorer Outcome in People With and Without Diabetes Hospitalized for COVID-19.

OBJECTIVE: Identifying metabolic factors associated with critical disease can help to improve management of patients hospitalized for coronavirus disease 2019 (COVID-19). High triglycerides and low HDL levels characterize the atherogenic dyslipidemia closely related to insulin resistance and diabetes. We examined associations of atherogenic dyslipidemia detected on admission with outcome of COVID-19 during hospitalization. RESEARCH DESIGN AND METHODS: We retrospectively analyzed clinical reports of 118 consecutive patients hospitalized for COVID-19 in Rome, Italy, between March and May 2020. Clinical characteristics, inflammation markers, and glucose and lipid metabolism parameters at admission were collected. Critical disease was defined as in-hospital death or need for endotracheal intubation. Associations were tested using logistic regression analysis. RESULTS: Patients with critical COVID-19 (n = 43) were significantly older than those with noncritical disease (n = 75) and presented higher levels of fasting glucose, triglycerides, C-reactive protein, interleukin-6, procalcitonin, and d-dimer (P < 0.01 for all), whereas HDL levels were lower (P = 0.003). Atherogenic dyslipidemia was more frequent in patients with critical COVID-19 (46 vs. 24%, P = 0.011), as well as diabetes (37 vs. 19%, P = 0.026), and significantly associated with death or intubation (odds ratio 2.53 [95% CI 1.16-6.32], P = 0.018). Triglycerides were significantly associated with selected inflammatory biomarkers (P < 0.05 for all) and poorer outcome of COVID-19 during hospitalization in both the overall population and the subgroup with atherogenic dyslipidemia. CONCLUSIONS: Atherogenic dyslipidemia detected on admission can be associated with critical in-hospital course of COVID-19. Further investigations are needed to elucidate the hypothetical role of insulin resistance and related lipid abnormalities in severe acute respiratory syndrome coronavirus 2 pathogenesis. Assessment of lipid profile should be encouraged in patients hospitalized for COVID-19.

Incidence of pneumomediastinum in COVID-19: A single-center comparison between 1st and 2nd wave.

In this study, we compared the incidence of pneumomediastinum in coronavirus disease (COVID-19) patients during the ascending phases of the 1st and 2nd epidemic waves. Crude incidence was higher during the 2nd wave at a quasi-significant level (0.68/1000 vs. 2.05/1000 patient-days, p = 0.05). When restricting the analysis to patients who developed pneumomediastinum during noninvasive ventilation, the difference became clearly significant (0.17/1000 vs 1.36/1000 patient-days, p = 0.039). At logistic regression, predisposing factors (p = 0.031), and COVID-19 radiological severity (p = 0.019) were independently associated with pneumomediastinum. Mortality in patients with pneumomediastinum was 87.5%. However, pneumomediastinum seemed to be related to a generally worse disease presentation in hospitalized patients during the 2nd wave, rather than to a separate pattern of disease.

Management of COPD patients during COVID: difficulties and experiences.

Introduction: The role of COPD in COVID-19 is not yet well understood. However, there is increasing evidence showing that COPD patients with COVID-19 have a higher risk of presenting a serious infection, a greater likelihood of requiring ICU support, and a higher mortality than other groups.Areas covered: In this article, we address some critical questions on COVID-19 as they pertain to COPD. In particular, we discuss whether the usual algorithms of pharmacological and non-pharmacological management in COPD still apply.Expert opinion: Patients with COPD must continue their regular therapy, regardless of whether they are affected by COVID-19. Corticosteroids reduce mortality in COVID-19 patients in need of supportive oxygen therapy or invasive mechanical ventilation. It is essential that a COPD patient who has tested positive for SARS-CoV-2 is closely followed over time because any delay in diagnosis and initiation of appropriate therapy could negatively affect his/her prognosis. However, we still do not know if COVID-19 infection occurs and evolves differently in each of the recognized COPD phenotypes and, therefore, whether it needs a different management. There are other open questions concerning COVID-19 and COPD that need to be considered. Future studies are absolutely necessary to answer these questions.

Disputes over the production and dissemination of misinformation in the time of COVID-19.

Ultimate coronavirus disease 2019 (COVID-19) mitigation and crisis resolution is dependent on trustworthy data and actionable information. At present time, there is still no cure for COVID-19, although some treatments are being used in severe illness. Regrettably, as the SARS-CoV-2 virus spreads, the lack of cure has been accompanied by an increasing amount of medical misinformation. In particular, there is a lot of misinformation about how to treat patients who have tested positive for SARS-CoV-2 and who are asymptomatic or have mild symptoms and for whom management at home is deemed appropriate. In this editorial, we highlight the risks deriving from this misinformation, which often arises from the publication of studies that are not conceptually and methodologically accurate.

SARS-CoV-2 Neutralizing Antibodies: A Network Meta-Analysis across Vaccines.

Background: There are no studies providing head-to-head comparison across SARS-CoV-2 vaccines. Therefore, we compared the efficacy of candidate vaccines in inducing neutralizing antibodies against SARS-CoV-2. Methods: A network meta-analysis was performed to compare the peak levels of SARS-CoV-2 neutralizing antibodies across candidate vaccines. Data were reported as standardized mean difference (SMD) since the outcome was assessed via different metrics and methods across the studies. Results: Data obtained from 836 healthy adult vaccine recipients were extracted from 11 studies. BBIBP-CorV, AZD1222, BNT162b2, New Crown COVID-19, and Sputnik V induced a very large effect on the level of neutralizing antibodies (SMD > 1.3); CoVLP, CoronaVac, NVX-CoV2373, and Ad5-nCoV induced a large effect (SMD > 0.8 to ≤1.3); and Ad26.COV2.S induced a medium effect (SMD > 0.5 to ≤0.8). BBIBP-CorV and AZD122 were more effective (p < 0.05) than Ad26.COV2.S, Ad5-nCoV, mRNA-1237, CoronaVac, NVX-CoV2373, CoVLP, and New Crown COVID-19; New Crown COVID-19 was more effective (p < 0.05) than Ad26.COV2.S, Ad5-nCoV, and mRNA-1237; CoronaVac was more effective (p < 0.05) than Ad26.COV2.S and Ad5-nCoV; and Sputnik V and BNT162b2 were more effective (p < 0.05) than Ad26.COV2.S. In recipients aged ≤60 years, AZD1222, BBIBP-CorV, and mRNA-1237 were the most effective candidate vaccines. Conclusion: All the candidate vaccines induced significant levels of SARS-CoV-2 neutralizing antibodies, but only AZD1222 and mRNA-1237 were certainly tested in patients aged ≥70 years. Compared with AZD1222, BNT162b and mRNA-1237 have the advantage that they can be quickly re-engineered to mimic new mutations of SARS-CoV-2.

Electrocardiographic modifications and cardiac involvement in COVID-19 patients: results from an Italian cohort.

AIM: The aim of this study was to detect predisposing CV risks factors and ECGs changes in COVID-19 patients. METHODS: The study population included 60 noncritically ill patients with COVID-19 pneumonia admitted to our hospital between 16 March and 11 May 2020. Electrographic changes, evaluated from ECGs acquired at admission and at 7 days after starting COVID-19 therapy, were analysed. We also compared 45 patients without CV involvement with 15 patients with new onset of cardiac adverse events during hospitalization. RESULTS: ECGs under treatment showed a lower heart rate (HR) (69.45 ±â€Š8.06 vs 80.1 ±â€Š25.1 beats/min, P = 0,001) and a longer QRS (102.46 ±â€Š15.08 vs 96.75 ±â€Š17.14, P = 0.000) and QT corrected (QTc) interval (452.15 ±â€Š37.55 vs 419.9 ±â€Š33.41, P = 0,000) duration than ECGs before therapy. Fifteen patients (25%) showed clinical CV involvement. Within this group, female sex, lower ejection fraction (EF), low serum haemoglobin, high Troponin I levels (TnI), low lymphocytes count, high serum IL-6 levels, or use of Tocilizumab (TCZ) were more represented. CONCLUSIONS: Patients admitted for SARS-CoV2 infection and treated with anti-COVID-19 drug therapy develop ECG changes such as reduction in HR and increase in QRS duration and QTc interval. One in four patients developed CV events. Gender, EF, heamoglobin values, TnI, lymphocytes count, IL-6 and use of TCZ can be considered as predisposing factors for CV involvement.

Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is characterized by immune-mediated lung injury and complex alterations of the immune system, such as lymphopenia and cytokine storm, that have been associated with adverse outcomes underlining a fundamental role of host response in severe acute respiratory syndrome coronavirus 2 infection and the pathogenesis of the disease. Thymosin alpha 1 (Tα1) is one of the molecules used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancer. METHODS: In this study, we captured the interconnected biological processes regulated by Tα1 in CD8+ T cells under inflammatory conditions. RESULTS: Genes associated with cytokine signaling and production were upregulated in blood cells from patients with COVID-19, and the ex vivo treatment with Tα1-mitigated cytokine expression, and inhibited lymphocyte activation in a CD8+ T-cell subset specifically. CONCLUSION: These data suggest the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.