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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus 2019 (COVID-19), which was declared a pandemic in March 2020 by the World Health Organization due the rapid spread representing a global health crisis. The disease is characterized by a wide clinical spectrum ranging from asymptomatic forms until severe viral pneumonia, which can to evolve to severe acute respiratory syndrome, especially in elderly patients and/or with comorbidities. An efficient assembly of the immunological response of the patients becomes fundamental against SARS-CoV-2 infection and it has been demonstrating a significant relationship between the severity of the disease and expression profile of the immune cells and the levels of pro-inflammatory cytokines. This review aims to presents the main immunological mechanisms developed during the infection by SARS-CoV-2 in the evolution of the severe cases of COVID-19. The immune dysregulation of the Th1 cellular response standard, the instability in the production of neutralizing antibodies by plasma B cells, the difference in tropism of CD8+ T cells against virus proteins in early infection, late infection and reinfections, dynamic of alveolar macrophages and pulmonary innate lymphoid cells (TCR γδ) of the natural imune response and the high level of pro-inflammatory cytokines can determine the main cause of breath tissues damages and, consequently, a greater severity of the disease. Therefore, a complete understanding of the main immunological changes involved in SARS-CoV-2 infection can identify possible biomarkers in the evaluation of early prognosis of the severe cases of COVID-19, making possible better therapeutic success to the patients.

Background: The CTD combination have both an immunomodulatory and immunosuppressive activity on multiplemyeloma (MM) patients (pts) treatment. The advance of immunotherapy has been demonstrated by the development ofnew agents like anti CD38-antibody Dara, that are increasing the overall and progression-free survival of MM pts. Daraeffect on the immune system was already described, but few studies analyzed specifically lymphocytes population. Wehypothesized that Dara-CTD combination could impact on lymphocytes subsets during treatment.Aims: The primary endpoint was to quantify subpopulations of lymphocytes in pts with newly diagnosed multiplemyeloma (NDMM) transplant eligible (TE) pts, during Dara-CTD treatment phases (induction, consolidation andmaintenance). Secondary endpoint was to describe B cells subsets during the same phases Methods: Peripheral blood of 14 pts at four different time points was collected: at diagnose, after four cycles of Dara-CTD, after two consolidation cycles post-autologous stem cell transplantation (ASCT) and before maintenance therapy.Flow cytometry was used to detect lymphocyte surface molecules including CD3, CD4, CD5, CD8, CD16, CD19, CD20,CD38, CD45 and CD56 in the scatter plot. B cells were isolated and subpopulations (naïve B cells, non-class switchedmemory B cells, class switched memory B cells, IgD-CD27- memory B cells and plasmablasts) were detected by CD20,CD24, CD27, CD38, CD45 and IgD. Statistics was performed using the SPSS®v25.0 Results: The pts median age was 55 range (41-65) years old, and 57% were female. The median of T, B and NKlymphocytes subsets at diagnosis were 1153 x 10³/μL, 205x 10³/μL and 284 x 10³/μL cells, respectively. After four cyclesof Dara-CTD the median of T, B and NK cells dropped significantly to 889 x 10³/μL, 12 x 10³/μL and 11 x 10³/μL,respectively (p

Background The CTD combination have both an immunomodulatory and immunosuppressive activity on multiple myeloma (MM) patients (pts) treatment. Dara, an antiCD38-antibody, effect on the immune system was already described, but few studies analyzed specifically lymphocytes population. We hypothesized that Dara-CTD combination could impact on lymphocytes subsets during treatment. The primary endpoint was to quantify subpopulations of lymphocytes in TE NDMM pts during Dara-CTD treatment phases. Secondary endpoint was to describe B cells subsets during the same phases. Methods Peripheral blood of 14 pts at four different time points was collected: at diagnose, after four cycles of Dara-CTD, after two consolidation cycles post ASCT and before maintenance therapy. Flow cytometry was used to detect lymphocyte surface molecules including CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. Results B cells were isolated and subpopulations (naive B cells, non-class switched memory B cells, class switched memory B cells, IgD-CD27- memory B cells and plasmablasts) were detected by CD20, CD24, CD27, CD38, CD45 and IgD. The median of T, B and NK lymphocytes subsets at diagnosis were 1153×103/µL, 205×103/µL and 284×103/µL cells, respectively. After 4 cycles of Dara-CTD the median of T, B and NK cells dropped significantly to 889×103/µL, 12×103/µL and 11×103/µL, respectively (p Conclusions This preliminary data suggest that Dara-CTD induces general lymphopenia on (T, B and NK) populations after induction phase. It was identified that T cells recovery was complete after two consolidations cycles while the recovery of B and NK cells was slowly but continuously.

Background: CD38-targeting antibody Daratumumab (Dara) has been demonstrating significant improvement in (MM) patient's survival. Cyclophosphamide (C), thalidomide (T) and dexamethasone (D) - (CTd) is one of the most used induction protocols worldwide and the MAX-Dara study was the first that combine Dara-CTd as induction for (NDMM) (TE) patients. We hypothesized that this new combo + autologous stem cell transplantation (ASCT) could affect the quantitative recovery of distinct lymphocytes subsets. Objective: Primary endpoint was to quantify lymphocytes subpopulations in (NDMM) (TE) patients at different treatment phases. Secondary endpoint was to evaluate B cells subsets at same times. Methods: Peripheral blood of 10 NDMM TE patients was collected at three different moments: at diagnose, after 4 induction cycles and after two consolidation cycles post- (ASCT). Dara-CTd protocol was for up to four 28-day induction cycles: C-500mg per oral (PO) d 1,8 and 15, T at 100-200mg PO d 1 to 28, Dex at 40mg PO d 1,8,15 and 22 and Dara 16mg/Kg/dose IV on d 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. Consolidation was started at D+30 after ASCT and all patients received up to four 28-day consolidation cycles: Dara 16mg/Kg and (D) at 40mg every other week, associated with T at 100mg PO d 1 - 28. Dara 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. Flow cytometry was used to detect lymphocyte surface by CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. B cells were isolated and subpopulations (naïve B cells, class and non-class switched memory B cells, , IgD-CD27- memory B cells and plasma blasts) were detected by CD20, CD24, CD27, CD38, CD45 and IgD. Statistical analysis was performed using the SPSS® v25.0. Results: The median number of lymphocytes subsets at diagnosis were 1139 x 10³/μL for T cells, 155 x 10³/μL for B cells and 284 x 10³/μL for NK cells. After four cycles of Dara-CTD the median number of T, B and NK cells had dropped to 834, 7.5 and 8.0 x 10³/μL respectively (p Disclosures De Queiroz Crusoe: Janssen: Research Funding.

Persistent immune actiation is associated with innadequate immune recovery in HIV-patients, This study assessed the relationship between frequency of expression of cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1 infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral treatment, were divided into three groups, according to the number of CD T cells and CD4+ / CD8+ ratio: adequate; partial; and inadequate immune restauration. All patients underwent full mouth assessments for saliva flow measurement, oral mucosal lesion, periodontal disease, and severity of periodontitis. Immune activation markers levels were compared according to three groups of periodontal disease (“No periodontal disease”; “gingivitis”; and “periodontitis”). Oral mucosal lesions (P = 0.03) and peridodontal disease (P = 0.03) were associated with lower CD4+/CD8+ ratio. Patients with oral mucosal lesions had significantly higher median levels of HLADR and CD38 markers in all T-lymphocytes populations than patients without oral lesions. Patients with gingivitis and with periodontitis presented significantly higher median levels of CD3+ HLADR+, CD4+ HLADR+, CD8+ HLADR+, and CD3+ CD38+ and significantly lower CD4+/CD8+ ratio than patients with no periodontal disease. Increased levels of HLADR and CD38 expressions in peripheral blood were associated with oral lesions in HIV-positive patients. Periodontal disease was associated with HLADR expression. This article is protected by copyright. All rights reserved

Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm3 within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r) was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm3 and 10 months to HIV-RNA to become undetectable. Keywords: HIV, acute infection, progression, AIDS

This study evaluated total lymphocyte count (TLC) as a substitute marker for CD4+ cell counts to identify patients who need prophylaxis against opportunistic infection (CD4200 cells/mm(3)) and patients with CD4350 cells/mm(3) (Brazilian threshold value of CD4 count to define AIDS). We evaluated TLC and CD4+ cells count of 1,174 HIV-infected patients, in Salvador, Brazil, from May 2003 to September 2004. CD4+ cell counts were performed by flow cytometry, and TLC was measured with an automated hematological counter. The mean CD4 count was 430 cells/mm(3) (range: 4 to 2,531 cells/mm(3)). Mean TLC was 1,900 cells/mm(3) (range: 300 to 6,200 cells/mm(3)). Using a threshold value of 1,000 cells/mm(3) for TLC, the positive predictive value (PPV) was 77% for CD4200 cells/mm(3), but the sensitivity was only 29%, while the negative predictive value (NPV) was 88%, with 98% specificity. Similar findings were observed for CD4 count350. Using the same threshold value of 1,000 cells/mm(3) for TLC, sensitivity was 14%, and specificity 99% (PPV= 94%; NPV=62%). In 70/1,510 (5%) of the samples the sum of CD4 and CD8 cell counts was greater than the TLC and in 27% (419/1,510) this sum was below 65% of the TLC. TLC has a high specificity to identify patients for prophylaxis, but a quite low sensitivity. It is not useful as an alternative to CD4+ T-cell counts as a marker in HIV-infected patients.