Persistent and fatal severe acute respiratory syndrome coronavirus 2 infection in a patient with severe hypogammaglobulinemia: a case report.

BACKGROUND: Viruses are constantly changing as a result of mutations, and new viral variants are expected to appear over time. The virus that causes coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, is not excluded from this condition. Patients with some types of immunodeficiency have been reported to experience symptoms that vary from mild to severe, or even death, after being infected with severe acute respiratory syndrome coronavirus 2. We report a case of a woman with severe hypogammaglobulinemia who developed a prolonged and fatal severe acute respiratory syndrome coronavirus 2 infection. CASE PRESENTATION: A 60-year-old mestizo female with a previous history of severe hypogammaglobulinemia manifested by recurrent pulmonary infections and follicular bronchiolitis. She received a monthly treatment of intravenous immunoglobulins and was admitted after report of a neurological manifestation related to a left thalamic inflammatory lesion, for a duration of 2 weeks of hospitalization, indicated for the study of her neurological condition, including brain biopsy. Both on admission and 1 week later, nasopharyngeal polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 were performed and reported negative. In the third week of hospitalization, she developed pulmonary symptoms, and a positive test result for severe acute respiratory syndrome coronavirus 2 was evidenced. On Day 3, the patients' condition worsened as the infection progressed to respiratory failure and required mechanical ventilation. On Day 8 after the coronavirus disease 2019 diagnosis, the polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 showed persistent detection of the virus. Various bacterial coinfections, including Klebsiella pneumoniae and Enterobacter cloacae, were diagnosed and treated. On Day 35, her pulmonary symptoms worsened, and the results of the severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test remained positive. On Day 36, despite all the respiratory support, the patient died. The severe acute respiratory syndrome coronavirus 2 virus was sequenced at the beginning and 8 days after the onset of the disease, and the strain, without obvious mutations in the gene that encodes spike protein, was identified. CONCLUSIONS: This clinical case showed persistent severe acute respiratory syndrome coronavirus 2 detection after 35 days of infection in a patient with severe hypogammaglobulinemia. The sequencing of the virus showed no mutations on the spike protein at 8 days, indicating that, in this case, the persistence of the viral detection was associated with immunodeficiency instead of changes in the viral components.

Systemic lupus erythematosus flare during SARS-CoV-2 infection: Report of 3 cases presented during the fourth wave of the pandemic in Colombia.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a worldwide pandemic since first discovered in 2019. Systemic lupus erythematosus (SLE) flare has been reported in the post-infectious period. In Colombia, the fourth pandemic wave started at the beginning of 2022 when we observed flare of 3 SLE patients during active infection. CASE PRESENTATION: We describe 3 patients with inactive SLE, who presented coronavirus disease 2019 and severe flare in early 2022, 2 patients with nephritis and 1 with severe thrombocytopenia. All patients had increase of antinuclear and anti-DNA antibody titers and complement consumption. CONCLUSIONS: Three cases with SLE flare concomitant with active SARS-CoV-2 infection were different from others reported earlier in the pandemic with post-infectious flare.

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It.

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals.

With the progression of the COVID-19 pandemic, there have been different reports about the development of autoimmune diseases once the infection is controlled. After entering the respiratory epithelial cells, SARS-CoV-2-the virus that causes the disease-triggers a severe inflammatory state in some patients known as "cytokine storm" and the development of thrombotic phenomena-both conditions being associated with high mortality. Patients additionally present severe lymphopenia and, in some cases, complement consumption and autoantibody development. There is a normalization of lymphocytes once the infection is controlled. After this, autoimmune conditions of unknown etiology may occur. A hypothesis for the development of post-COVID-19 autoimmunity is proposed based on the consequences of both a transient immunosuppression (both of innate and acquired immunity) in which self-tolerance is lost and an inappropriate form of immune reconstitution that amplifies the process.

Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19.

In December 2019, a new and highly contagious infectious disease emerged in Wuhan, China. The etiologic agent was identified as a novel coronavirus, now known as Severe Acute Syndrome Coronavirus-2 (SARS-CoV-2). Recent research has revealed that virus entry takes place upon the union of the virus S surface protein with the type I transmembrane metallo-carboxypeptidase, angiotensin converting enzyme 2 (ACE-2) identified on epithelial cells of the host respiratory tract. Virus triggers the synthesis and release of pro-inflammatory cytokines, including IL-6 and TNF-α and also promotes downregulation of ACE-2, which promotes a concomitant increase in levels of angiotensin II (AT-II). Both TNF-α and AT-II have been implicated in promoting overexpression of tissue factor (TF) in platelets and macrophages. Additionally, the generation of antiphospholipid antibodies associated with COVID-19 may also promote an increase in TF. TF may be a critical mediator associated with the development of thrombotic phenomena in COVID-19, and should be a target for future study.