Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-α. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.

Long-term effects of COVID-19 in diabetic and non-diabetic patients.

The literature presents several reports of the impact of glycemic control and diabetes in the inflammatory and coagulatory response during coronavirus disease 2019 (COVID-19). Nevertheless, the long-term impact of the COVID-19 in diabetic patients is still to be explored. Therefore, we recruited 128 patients and performed a longitudinal analysis on COVID-19-associated biomarkers of patients with COVID-19, tree and 6 months after COVID-19 recovery and put into perspective the possible long-term complication generated after COVID-19. In our investigation, we failed to verify any long-term modification on inflammatory biomarkers, but detected an increase in the glycemia and glycated hemoglobin in patients without any pre-existing history or diagnosis of diabetes (non-diabetic patients). Although diabetic and non-diabetic patients presented elevated levels of glycated hemoglobin, the c-peptide test indicated a normal beta cell function in all patients.

Effectiveness of the Inactivated SARS-CoV-2 (Vero Cell) Vaccine in Peruvian Health Workers.

INTRODUCTION: The COVID-19 pandemic has caused a global health crisis. Vaccines against this disease have demonstrated variable efficacy and safety, although effectiveness has not been evaluated. In February 2021, the Ministry of Health of Peru approved the emergency use of the inactivated SARS-CoV-2 (Vero Cell) vaccine and initiated vaccination with health personnel at the national level. The objective of the study is to determine the effectiveness of this vaccine to reduce infections, hospitalizations, and deaths due to COVID-19. METHODOLOGY: We performed a retrospective cohort study in the period from 23 February to 26 June 2021; data were obtained from the Ministry of Health (including demographic, epidemiologic, clinical, hospital, laboratory results, deaths, and both date and quantity of vaccine doses delivered). The exposed cohort were those who received one or two vaccine doses and the non-exposed were unvaccinated. The events studied were infections, hospitalizations and deaths in the cohorts. We consider a case confirmed for COVID-19 if the test result was positive for SARS-CoV-2, via PCR or antigen test. Effectiveness was measured with incidence density ratio and risk. Confounding factors were controlled using a Poisson model with robust variance. RESULTS: We enlisted 520,733 health workers, of whom 415,212 had two vaccine doses and 105,521 were unvaccinated. The median age was 40 years (IQR: 32-50), and 65.6% were female. The effectiveness of two vaccine doses fourteen days after application adjusted by age, sex, hospitalization, and antecedent of having the infection was 90.9% (95% CI: 85.5-94.2%); effectiveness to avoid death from COVID-19; 67.7% (60.1-73.8%) effectiveness to avoid hospitalizations; and 26.3% (23.8-28.6%) effectiveness to reduce the risk of infection by SARS-CoV-2 relative to the unvaccinated cohort. CONCLUSIONS: The inactivated SARS-CoV-2 (Vero Cell) vaccine used in two doses has an acceptable effectiveness against death and risk of hospitalization, whereas it has less effectiveness in preventing COVID-19 infection.

Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity.

COVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.

Role of vitamin D deficiency and comorbidities in COVID-19.

Recent manuscripts described the incidence of vitamin D hypovitaminosis in coronavirus disease 2019 (COVID-19) patients. Vitamin D deficiency is also common in patients with comorbidities that are associated with a poor COVID-19 prognosis. In this letter, we review the literature regarding the association of comorbidities, vitamin D deficiency, and COVID-19.

SARS-CoV-2 infection in liver transplant recipients: A complex relationship.

The recent manuscript reviewed investigations involving liver damage in coronavirus disease 2019 (COVID-19) patients, and COVID-19 in patients with previous chronic hepatological diseases, such as patients with liver graft. The literature presents several conflicting results concerning the anti-SARS-CoV-2 response in patients with solid organ transplants, in liver transplant recipients. Therefore, we would like to humbly state a few points for consideration involving liver transplant recipients and COVID-19, such as the time since transplantation, comorbidities, and immunosuppressive regimens.

Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients´ outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.

COVID-19 Severity and Mortality in Solid Organ Transplantation: Differences between Liver, Heart, and Kidney Recipients

The infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can generate a wide spectrum of clinical manifestations ranging from asymptomatic to severe respiratory and systemic disease with coagulation disorder named coronavirus disease 2019 (COVID-19). Patients with comorbidities have been identified as risk groups for severe COVID-19, also having a higher death risk. Previous reports have conflicting results regarding if solid organ transplant recipients present an increased risk for COVID-19. Nevertheless, previous investigations failed to distinguish between different organs received or made a longitudinal investigation on those patients. We recruited 39 solid organ transplant recipients: 25 kidney transplant recipients, 7 heart transplant recipients, and 7 liver transplant recipients and 25 age-matched non-transplant COVID-19 patients without comorbidities (control group) and compared daily laboratory data in addition to performing survival analysis. Heart and kidney transplant recipients presented an increase in several COVID-19 severity-associated biomarkers, such as neutrophil-to-lymphocyte ratio and thrombocytopenia, in comparison to the control group and liver transplant recipients. Heart and kidney transplant recipients also presented an increase in the need for intensive care and invasive mechanical ventilation during the disease’s course. Importantly, heart and kidney transplant recipients presented a higher mortality rate in comparison to liver transplant recipients and non-transplant recipients. In our cohort, heart and kidney transplant recipients presented a difference in clinical characteristics and survival rate in comparison to liver transplant recipients. Further investigation involving immune response to SARS-CoV-2 in solid organ recipients should consider and separate patients according to the organ grafted.

Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease-2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.

Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19.

Psoriasis is an immune-mediated dermatosis usually associated with comorbidities. Treatment varies from topicals to systemic drugs and data on susceptibility to viral infections in psoriatic patients are scarce. The objectives of this study were to analyze psoriatic patients on different therapies who were at risk for COVID-19 for seroprevalence of SARS-COV-2, pro-inflammatory cytokine profile, comorbidities and outcomes in order to unveil the immunological mechanisms involved in the anti-viral response in patients with psoriasis. Seventy-five patients with psoriasis were divided according to treatment: immunobiologics, methotrexate, topicals and acitretin. Twenty healthy controls were included. Plasma samples were collected for: IgG SARS-COV-2 (ELISA); IL-27, IL-29 and IL-18 (ELISA); and IL-1ß, IL-17A, IL-6 and TNF (cytometric array). Seropositivity for SARS-COV-2 was detected in 24 out of 75 psoriasis patients and did not relate to COVID-19 symptoms and/or hospitalization, despite associated comorbidities. Psoriasis patients who were asymptomatic for SARS-COV-2 exhibited immune imbalance with high levels of IL-18, IL-17A and IL-6, and low levels of IL-27 compared to healthy controls. Psoriasis groups showed significant increased cytokine levels only in the group with immunobiologics. Despite immune deviations and lower IL-27, which has a potential antiviral impact, psoriatic patients did not exhibit complications related to COVID-19. An understanding of this kind of proinflammatory profile of psoriatic patients and of the lack of severe outcomes for COVID-19 is essential to establish novel therapeutic approaches and preventive measures, including with regard to the concomitance of viral infections.

Coronavirus disease-2019 and the intestinal tract: An overview.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can progress to a severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19). The most common symptoms are fever and respiratory discomfort. Nevertheless, gastrointestinal infections have been reported, with symptoms such as diarrhea, nausea, vomiting, abdominal pain, and lack of appetite. Importantly, SARS-CoV-2 can remain positive in fecal samples after nasopharyngeal clearance. After gastrointestinal SARS-CoV-2 infection and other viral gastrointestinal infections, some patients may develop alterations in the gastrointestinal microbiota. In addition, some COVID-19 patients may receive antibiotics, which may also disturb gastrointestinal homeostasis. In summary, the gastrointestinal system, gut microbiome, and gut-lung axis may represent an important role in the development, severity, and treatment of COVID-19. Therefore, in this review, we explore the current pieces of evidence of COVID-19 gastrointestinal manifestations, possible implications, and interventions.

SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.

COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients.

The severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.

Case Report: COVID-19 and Chagas Disease in Two Coinfected Patients.

American trypanosomiasis, also named Chagas disease (CD), is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi. The disease affects millions of people worldwide, leading yearly to approximately 50,000 deaths. COVID-19, generated by SARS-CoV-2, can lead to lymphopenia and death. We hereby describe the first report of two patients with CD and COVID-19 coinfection, from hospitalization until patients' death.