SARS-CoV-2 Incidence, signs and symptoms and main risk factors for COVID-19 infection in Health Care Workers: A hospital-wide survey in Salvador, Brazil

ABSTRACT Background: Brazil is the third country most affected by Coronavirus Disease 2019 (COVID-19) in the world. Health care workers (HCWs) are at higher risk of infection. Despite the increasing numbers of studies on the topic, There are gaps in the knowledge of characteristics and risk factors for infection of HCWS. This information is important to design preventive strategies and to mitigate the disease impact. The objective of this study was to estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to identify factors associated, and to describe symptoms reported by healthcare workers at a tertiary hospital in Salvador, Brazil. Methods: All HCWs were evaluated in a cross-sectional study conducted between May and September 2020, using self-administered questionnaires, and screening all participants for SARS-COV-2 IgG and IgM antibodies by rapid tests. Reactive IgG samples were retested by ELISA and IgM-positive test had a saliva sample retest by RT-PCR. Univariate associations were estimated by a non-adjusted incidence proportion ratio. Variables associated with COVID-19 incidence at p < 0.20 were selected for inclusion in a binary logistic regression model. Results: A total of 2083 HCWs were included, mean age 41±10 years, 71.8% women, and 77.8% non-white. Of these, 271 (13.0%) and 25 (1.2%) HCWs tested positive for IgG and IgM SARS-CoV-2 antibodies, respectively, and three had a positive RT-PCR. Ancillary work [Odds Ratio (OR): 4.96], elementary education (OR: 2.91), high school education (OR: 2.89), and catholic religion (OR: 2.16) were associated with an increased likelihood of a positive IgG antibodies against SARS-CoV-2. Anosmia [Incidence Proportion Ratio (IPR): 7.41] and ageusia (IPR:8.51) were the most frequent associated symptoms. Conclusion: HCWs with low mean family income, lower level of schooling, ancillary workor being black had a significantly higher likelihood of testing positive for SARS-CoV-2 antibodies. Social vulnerability was an important risk factor for COVID-19 infection.

Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response

ABSTRACT Background: Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common, despite the lack of evidence on its clinical efficacy. Objective: To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers (HCW) diagnosed with COVID-19 and of Th1/Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort (PBMCs). Methods: This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universitário Professor Edgard Santos (Salvador, Brazil), diagnosed with COVID-19 from May to July, 2020, as well as in vitro production of antibody against SARS-CoV-2 and Th1/Th2 cytokines. Analyses were performed between December 2020 and February 2021. Participants were stratified according to the use of ivermectin (≤ 1 dose vs. multiple doses) for treatment of COVID-19. Results: 45 HCW were included (62% women). Mean age was 39 years, and disease severity was similar across groups. Neutralizing antibodies were detected less frequently in multiple doses (70%) vs. ≤ 1 dose (97%) groups, p = 0.02). PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following in vitro stimulation with purified spike protein in comparison with patients in ≤ 1 dose group (p < 0.001). PBMC's production of Th1/Th2 cytokines levels was similar across groups. Abdominal pain (15% vs 46%, p = 0.04), diarrhea (21% vs. 55%, p = 0.05) and taste perversion (0% vs. 18%, p = 0.05) were more frequently reported by participants that used multiple doses of ivermectin. Conclusions: Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production, in a dose dependent manner. This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects.

HLA-B*14 allele predicts HIV-1 mother-to-child-transmission, in Salvador, Brazil

ABSTRACT Background: Class I human leukocyte antigens, especially the molecules encoded at the B locus (HLA-B), are associated with AIDS progression risk. Different groups of HLA-B alleles have been associated to a protective effect or increasing susceptibility to HIV infection and are expressed from the earliest stages of gestation. Objective: The aim of this study was to evaluate which variants of HLA-B are associated with the risk of HIV vertical transmission in infected pregnant women and in their offspring, in a referral center in Salvador Bahia. Methods: We performed HLA-B genotyping in 52 HIV-infected mothers and their children exposed to HIV-1 during pregnancy (N = 65) in Salvador, Brazil. We compared the HLA-B alleles frequency in mothers, uninfected and infected children, according to the use of antiretroviral prophylaxis. Results: Absence of antiretroviral antenatal and postnatal prophylaxis was significantly associated with vertical transmission of HIV-1 (p = <0.01, and p = <0.01 respectively). Frequency of HLA-B*14 (29.2%, p = 0.002), HLA-B*18 (16.7%, p = 0.04) or HLA-B*14:1 (20.8%, p = 0.01) alleles subgroups were significantly higher in HIV-1 infected children and persisted (HLA-B*14, p = 0.04) even after adjusting for use of antiretroviral prophylaxis. No significant difference in expression of HLA-B alleles was observed among mothers who transmitted the virus compared to those who did not. Conclusions: Expression of HLA-B*14 allele in children exposed to HIV-1 is predictive of vertical transmission and reinforces the important role of genetics in mother-to-child transmission.

A systematic review on the influence of hla-b polymorphisms on hiv-1 mother-to-child-transmission

ABSTRACT Background: Mother-to-child-transmission (MTCT) is the main route of HIV-1 infection in children. Genetic studies suggest HLA-B alleles play an important role on HIV-1 transmission, progression, and control of HIV-1 infection. Objective: To evaluate which polymorphisms of HLA-B are involved in HIV-1 MTCT. Methods: Two independent reviewers performed a systematic review on search engines PubMed, Europe PMC, Cochrane, Scientific Electronic Library Online (SciELO), and Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs), using the following key terms: "HIV infection", "HIV newborn", "HLA polymorphisms", "HLA-B", and "Mother to child transmission". All studies focusing on evaluation of HIV-1 MTCT, HIV infection evolution, and molecular analyses of HLA-B in children were selected. Results: Nine studies fulfilled the inclusion criteria. Sixteen HLA-B alleles groups were associated with HIV-1 infection; seven of them (43.8%) were related to slow disease progression or reduced risk of MTCT, while six (37.5%) alleles groups were linked to a faster progression of HIV infection in children and to increased risk of MTCT. The available evidence suggest that HLA-B*57 group allele is associated with slow disease progression, while HLA-B*35 group allele is associated to increased risk of MTCT and rapid disease progression in infected children. The role of HLA-B*18, B*58 and B*44 are still controversial because they were associated to both, protection against MTCT, and to higher HIV replicative capacity, in different studies. Conclusion: HLA-B*57 group allele can be protective against MTCT while HLA-B*35 groups alleles are consistently associated with HIV-1 MTCT.

Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing antiretroviral therapy

We analyzed the first 96 patients tested for HIV resistance to antiretroviral therapy in three Brazilian states. The HIV-1 reverse transcriptase (RT) and protease (PR) were sequenced by using the ABI ViroSeq system. The drugs previously used for each patient were recorded and correlated with the mutations found in the samples. Viral load (VL) and CD4 count were also recorded. Only one patient had the wild type sequence. The most prevalent mutations were: 184V (59 percent), 41L (47.9 percent), 63P (53 percent), 215Y (50 percent), 36I (46 percent), 10I (35 percent), 67N (42 percent), 77I (37 percent), 90M (36 percent) and 210W (33 percent). A positive correlation between the number of previously used ARVs and the number of mutations was observed (p<0.05). Associations between mutations and ARV drugs were identified at positions 69, 118, 184 and 215 with previous exposure to NRTI, mutations at positions 98, 100, 103, 181 and 190 with previous NNRTI use and at positions 10, 20, 30, 46, 53, 54, 71, 73, 82, 84, 88 and 90 with previous PI therapy (p<0.05). Previous exposure to ARV drugs was associated with previous genotypic resistance to specific drugs, leading to treatment failure in HIV patients. Genotypic resistance was clearly associated with virological and immunological failure.

No evidence of vertical transmission of HTLV-I in bottle-fed children

The most frequent pathway of vertical transmission of HTLV-I is breast-feeding, however bottle fed children may also become infected in a frequency varying from 4 to 14 percent. In these children the most probable routes of infection are transplacental or contamination in the birth canal. Forty-one bottle-fed children of HTLV-I seropositive mothers in ages varying from three to 39 months (average age of 11 months) were submitted to nested polymerase chain reaction analysis (pol and tax genes). 81.5 percent of the children were born by an elective cesarean section. No case of infection was detected. The absence of HTLV-I infection in these cases indicates that transmission by transplacental route may be very infrequent

Use od standard therapy for tuberculosis in associated with increased adverse reactions in patients with HIV

Hepatitis due to anti-tuberculosis therapy in an infrequent, but potentially devastating event. In HIV positive patients with tuberculosis (TB), the consequences are likely to be even greater, as they frequently require other hepatoptoxic medications. The object of our study was to determine the frequency to toxic hepatitis during therapy for TB. Included were 198 patients with a presumed or confirmed diagnosis of tuberculosis; of whom, 69 were HIV positive (35 percent), 75 were negative (38 percent) and 54 had unknown HIV status (27 percent). Toxic hepatitis occurred in 15/198 (8 percent) patients. The incidence of hepatitis in HIV patients was much greater than in HIV negative/unknown [RR=7.5 (2.2-25.6); p=0.0001] and the onset of hepatitis was short (median 7 days in HIV patients). During TB therapy, 1 in 8 (12.5 percent) patients taking ketoconazele developed hepatitis; 9/53 (17 percent) taking sulfamethoxazole-trimethoprim [RR=3.4 (1.1-9.3); p=0.03]. Among the 15 patients who developed hepatitis 11 required hospitalization (mean 19 days), 5 dfied (33.3 percent), 2/15 (13 percent) due to hepatitis. HIV positive patients had a significantly higher rate of toxic hepatitis during anti-tuberculosis therapy than those without HIV infection. Hepatitis occurred just after initiation of TB treatment. Clinical findings were non-specific and hepatic enzyme elevations were moderate, yet hospitalization and mortality rates were high. This suggests that in settings where careful monitoring of patients early in their course of TB treatment is routine, morbibity and mortality may be loe, but poor monitoring would have potentially serious consequences. There is a need for new drug treatments (schedules or regimens) for TB in an effort to reduce these adverse events.

Prospective evaluation of in vitro prodution of HIV-1 specific antibodies (IVAP), p24 antigenemia and viral culture for the diagnosis of HIV infection in children born to HIV-1 infected mothers

Three methods (IVAP, p24 antigenemia and viral cultivatio) for the diagnosis of HIV-1 infection among children born to HIV-1 infected mothers were prospectively evaluated to determine the applicability of IVAP as a useful technique for that purpose. We tested 15 children (8p0 and 7 pII) and 19 adults with well-estabilished serological status for HIV infection. The children were followed for at least 1 year, unless they developed symptoms of clinical AIDS, or their HIV serology became negative. The IVAP method was more sensitive and specific than the other 2 tests in determining whether or not the infants were infected with HIV. All negative test results (5/8) were confirmed during the same time period. Despite the small sample studied, we conclude that IVAP is in inexpensive and simple technique potentially useful to establish whether or not HIV-seropositive children born to infected mothers are HIV infected.

Co-infection of tuberculosis and HIV/HTLV retroviruses: Frequency and prognosis among patients admitted in a Brazilian hospital

During 2½ year period, 378 patients diagnosed with tuberculosis and admitted to a general hospital for care of the poor in Salvador, Bahia, were tested serologically for HIV-1, HTLV-I, and HTLV-II. The patients' mean age was 41.8 (range 14-89); they were hospitalized for a mean of 62 ñ 43 days; 70 percent were being treated for the first time; most of the remainder were being retreated after non-compliance with previously recommended anti-tuberculosis medication and a few required second-line therapy for relapsed disease. None had had previous serologic testing for retroviruses. Among the study population, 59 (16 percent) were found to be positive for retroviral infection. The distribution was as follows: 18 (4.8 percent) had HIV-1, 32 (8.5 percent) had HTLV-I, 2 of these had both HTLV-I and HTLV-II, 9 (2.4 percent) had both HIV-1 and HTLV-I. The rates of positive serologic tests for retroviral infection in this Salvador is 0.2 percent for HIV-1 and 1.0 percent for HTLV-I. Thus, there is a higher than expected frequency of retroviral infections among patients hospitalized for treatment of tuberculosis. The prognosis for treated patients was determined by recording the cause of death and the mortality rate. In the 319 patients with negative serologic testing for retroviruses the were 25 death (8 percent). In 32 patients with HTLV-I infection there were 8 death (25 prcent), and in 18 patients with HIV-1 infection there were 6 deaths (33 percent). In 9 patients with both HIV-1 and HTLV-I there were 5 deaths (56 percent). The causes of death in each serological group were primarily related to progression of tuberculosis rather than complications of rapid progression of the retroviral infection. We conclude that co-infection and disease due to either HIV-1 or HTLV-I/II infection and tuberculosis is common, that the ocurrence of HTLV-I in this population is higher than previously recognized, and that prognosis associated with the management of tuberculosis is adversely affected by the presence of either retroviral infection. In a few patients with both retroviral infections, mortality was very high. All patients with tuberculosis should be tested for retroviral infection because of the prognostic and therapeutic implications.

Epidemiological characteristics of HTLV-I and II co-infection in Brazilian subjects infected by HIV-1

Serum samples from 895 HIV-1 infected individuals were tested for antibodies against HTLV-I and HTLV-II. The overall prevalence of the co-infection was high (16.3 percent). Epidemiological information was obtained from each subject including gender, age, intravenous drug use (IVDU), blood transfusion, previous diagnosis of sexually transmitted diseases (STD) and sexual behavior. The risks for acquiring retroviral infections other than HIV-1 were evaluated and the prevalence of co-infection was compared according to the AIDS clinical status. We detected seven cases (0.9 percent) of triple infection. HTLV-I co-infection was associated with blood transfusion (p=0.009). Women co-infected by HTLV-I or HTLV-II had a higher risk of AIDS than those infected only by HIV-1 (RR=2.04; 95 percent CI: 1.27-3.27, p=0.007 and RR=3.09; 95 percent CI: 1.07-8.91, p=0.04, respectively). These findings suggest that co-infection by HTLV-I or II in Bahia, Brazil, may modify the clinical course of HIV-1 infection.

The influence of CD4+ T cells, HIV disease stage and zidovudine on HIV isolation in Bahia, Brazil

HIV-1 isolation was attempted on 72 individuals, including persons with known HIV infection and five without proven HIV infection but with indeterminate Western blot patterns, as well as on low-risk HIV seronegative persons. The ability to detect HIV-1 from culture supernatant by p24 antigen capture assay was evaluated by segregating patients by absolute CD4+ cell counts, clinical stage of disease, p24 antigenemia and zidovudine use. The likelihood of a p24 positive HIV culture was highest among patients with CD4+ T-cell counts below 200/ul and patients with advanced clinical disease. Use of zidovudine did not affect the rate of HIV positivity in cultures.