Cryptococcal meningitis post-covid-19 infection: Immunomodulation, a double-edged sword.

Cryptococcal meningitis is an opportunistic infection associated with altered immunity. Immunomodulatory agent use in severe coronavirus disease 2019 (COVID-19) may predispose such infections. Here, we present a 75-year-old male patient who presented with fever and altered general status after severe COVID-19 infection and developed cryptococcal meningitis. Opportunistic infection may arise from the use of immunomodulation in severe COVID-19, especially in the elderly population. This article describes the case and extensively reviews cryptococcal disease post-COVID-19 literature, highlighting the risk from immunosuppressive treatment.

COVID-19 infection and seroconversion rates in healthcare workers in Lebanon: An observational study.

Coronavirus disease 2019 (COVID-19) infection is a recent pandemic. Healthcare workers (HCW) are at high risk of acquiring the infection and transmitting it to others. Seroprevalence for COVID-19 among HCW varies between countries, hospitals in the same country and even among different departments in the same hospital. In this study, we aim to determine the prevalence of severe acute respiratory syndrome coronavirus 2 antibodies and the seroconversion among the HCW in our hospital. A total of 203 HCW were included. The rate of conversion to seropositive was 19.7% in total, with a rate of 13.4% in female versus 25% in male. The seropositivity in the House keeping group was 83%, followed by 45% in the COVID Floor while the seropositivity in the Anesthesia was 4% and the Infection Control 0%. The highest seropositivity rate in the COVID floor, and in the intensive care unit was explained by the long time spent with the patients. While in the inhalation team and the anesthesia, the lower rates of seropositivity was due to the N95 mask wearing the whole time. Seropositivity for COVID-19 in HCW is a major public health concern. Policies should be implemented to better protect HCWs.

The current challenges affecting the quality of care of HIV/AIDS in the Middle East: Perspectives from local experts and future directions.

OBJECTIVE: This report aimed to reflect the experts' views regarding the challenges affecting the quality of care for people living with HIV in the Middle East. Besides, we integrated experts' opinions and recommendations to offer future directions to improve the quality of care and the overall landscape of HIV in the Middle East. METHODS: This review article is based on a comprehensive literature search and the outcomes of several regional meetings that discussed the challenges faced by patients living with HIV in the Middle East. RESULTS: The experts called for actions by various stakeholders to improve the quality of HIV care and implement culturally acceptable programs to face the ongoing stigma and discrimination. Various strategies should also be implemented to improve the HIV awareness among the general population and medical staff, prompt early diagnosis and initiation of ART,and optimize patients' adherence to treatment. Besides, reliable databases, both on national and regional scales, should be implemented to provide reliable data regarding the HIV status in the region. CONCLUSION: All efforts should be directed towards achieving the UNAIDS the "90-90-90" targets, with an acceptable quality of life and minimal complications.

Intravenous high dose vitamin C and selected antiviral drugs in hospitalized COVID-19 patients: a descriptive cohort study.

INTRODUCTION: There is lack of universal agreement on the management of COVID-19. Intravenous high dose vitamin C (HDVC), remdesivir (RDV), and favipiravir (FPV) have been suggested as part of the treatment regimens and only RDV is approved by the Food and Drug Administration (FDA) so far. There is no study in Lebanon that addresses the descriptive cohort of HDVC and antiviral therapy amongst COVID-19 inpatients. Our goal was to highlight such a cohort. METHODOLOGY: A retrospective electronic chart review of COVID-19 inpatients was done over a period of 10 months (August 2020 to April 2021). Comparative data analysis was performed between HDVC and non-HDVC (NHDVC) groups, and RDV and FPV groups. RESULTS: Among HDVC patients, 70.1% (p = 0.035) and 67.2% (p = 0.008) had dyspnea and desaturation respectively. Patients on HDVC were less likely to remain in hospital for more than 20 days (p = 0.003). HDVC patients were more likely to be on oxygen therapy with 74.7% (p = 0.002). RDV patients were more likely to be on other COVID-19-related medications during hospitalization including the use of tofacitinib, baricitinib, tocilizumab, and anticoagulation as recommended in the guidelines. Statistical significance was noted for the status on discharge as 90.1% of the patients that received RDV were discharged after clinical improvement, compared to the 74.2% of the FPV patients. CONCLUSIONS: Further research is needed to establish local guidelines for the treatment of COVID-19. A significant role of HDVC and FPV might resurface if randomized control trials are conducted.

The effect of the BNT162b2 vaccine on antinuclear antibody and antiphospholipid antibody levels.

The Food and Drug Administration (FDA) approved the first SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) in December 2020. New adverse events have emerged since these vaccines have reached market. Although no clear association between messenger ribonucleic acid (mRNA) vaccines and autoimmunity has emerged, the significance of such an association warrants further exploration. After obtaining consent, a standardized survey on baseline characteristics and other relevant variables was conducted on unvaccinated individuals who were scheduled for vaccination and had not previously contracted COVID-19. Blood samples were collected from participants prior to the first dose, prior to the second dose, and 1 month after the second dose. All collected samples were tested for antinuclear antibody (ANA) titers using indirect immunofluorescence microscopy kits, and antiphospholipid (APS) immunoglobulin M (IgM) and immunoglobulin G (IgG) levels using an enzyme-linked immunoassay (ELISA) technique. ANA titers were positive for 9 participants out of 101 (8.9%) in the first pre-vaccination draw. For the second draw, the number of participants testing positive for ANA decreased to 5 (5%). For the last draw, 6 (5.9%) participants tested positive for ANA titers. One participant tested positive for APS IgM at the first pre-vaccination draw, 2 tested positive at the second draw, and 2 at the third draw. As for APS IgG titers, all participants tested negative in the three draws. McNemar's test for two dependent categorical outcomes was conducted on all variables and did not show a statistical significance. The McNemar test of these two composite variables (i.e., ANA/APS, first draw vs. ANA/APS, second and third draws) did not show statistical significance. The 2-sided exact significance of the McNemar test was 1.0. The Friedman test also showed no significance (p = 0.459). No association was found between BNT162b2 vaccine administration and changes in APS and ANA titers. The benefits of the BNT162b2 vaccine significantly outweigh any possible risk of autoimmune dysregulation considering the current evidence.

Managing endothelial dysfunction in COVID-19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Coronavirus disease 2019 (COVID-19) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortality. In this pilot, double-blind, placebo-controlled, randomized clinical trial, we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID-19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L-arginine, folate, Nebivolol, and atorvastatin) or placebo for up to 14 days. The primary outcome was time to recovery, measured by an eight category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection-control or other nonmedical reasons. Secondary outcomes included the composite outcome of intensive care unit (ICU) admission or the need for mechanical ventilation, all-cause mortality, and the occurrence of side effects. Of 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57 years; the mean body mass index of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and diabetes mellitus in 21.6%. The median (interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4-12] days) and the placebo group (6 [5-8] days; p value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all-cause mortality, or the occurrence of side effects between the endothelial protocol group and the placebo group. Among patients hospitalized with mild, moderate, or severe COVID-19 infection, targeting endothelial dysfunction by administering Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. Based on this study's findings, targeting endothelial dysfunction did not result in a clinically significant improvement in outcome and, as such, larger trials targeting this pathway are not recommended.

Prevalence and determinants of SARS-CoV-2 neutralizing antibodies in Lebanon.

According to the Lebanese Ministry of Public Health, more than 1,053,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been confirmed in Lebanon so far. The actual number of cases is likely to be higher. We conducted a serological study from October 2020 to April 2021 to estimate the prevalence of SARS-CoV-2 neutralizing antibodies and identify associated factors. Serum samples as well as demographic, health, and behavioral data were collected from 2,783 subjects. Sera were tested by microneutralization assay. Neutralizing antibodies were detected in 58.9% of the study population. The positivity rate increased over the study period. It was highest among the group who remained at work during the COVID-19 pandemic and in peri-urban areas with limited adherence to preventive measures. Sex and age were associated with positivity. Reported previous COVID-19, exposure to a COVID-19 patient in the family, and attending gatherings were associated with increased prevalence. Not taking any precautionary measures against COVID-19 was a risk factor, whereas precautionary measures such as working from home and washing hands were protective. The high neutralizing antibody seroprevalence rates detected in this study emphasize the high transmission rate of SARS-CoV-2 infection in the community. Adherence to preventive measures and non-pharmaceutical interventions imposed by the government is recommended.

Lebanese SARS-CoV-2 genomics: 24 months of the pandemic.

The COVID-19 pandemic continues to pose a global health concern, despite the ongoing vaccination campaigns, due to the emergence and rapid spread of new variants of the causative agent SARS-CoV-2. These variants are identified and tracked via the marker mutations they carry, and the classification system put in place following tremendous sequencing efforts. In this study, the genomes of 1,230 Lebanese SARS-CoV-2 strains collected throughout 2 years of the outbreak in Lebanon were analyzed, 115 of which sequenced within this project. Strains were classified into seven GISAID clades, the major one being GRY, and 36 Pango lineages, with three variants of concern identified: alpha, delta and omicron. A time course distribution of GISAID clades allowed the visualization of change throughout the two years of the Lebanese outbreak, in conjunction with major events and measures in the country. Subsequent phylogenetic analysis showed the clustering of strains belonging to the same clades. In addition, a mutational survey showed the presence of mutations in the structural, non-structural and accessory proteins. Twenty five (25) mutations were labeled as major, i.e. present in more than 30% of the strains, such as the common Spike_D614G and NSP3_T183I. Whereas 635 were labeled as uncommon, i.e. found in very few of the analyzed strains as well as GISAID records, such as NSP2_I349V. Distribution of these mutations differed between 2020, and the first and the second half of 2021. In summary, this study highlights key genomic aspects of the Lebanese SARS-CoV-2 strains collected in 2020, the first year of the outbreak in Lebanon, versus those collected in 2021, the second year of COVID-19 in Lebanon.

Severe acute respiratory syndrome coronavirus 2 antibody seroprevalence in Lebanon: a population-based cross-sectional study.

Objectives: The World Health Organization has promoted the use of serological testing as a rapid and accurate technique for the detection of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Lebanon, a better understanding of the immune response against SARS-CoV-2 is needed to develop effective measures for prevention and to plan an appropriate national vaccination program. This study aimed to measure the immunity status in Lebanon. Methods: In this cross-sectional study, the population comprised male and female Lebanese and non-Lebanese residents of Lebanon between the ages 15 and 75. The exclusion criteria included: same household, symptomatic individuals, and extremes of age (< 15 and > 75). Representative testing for SARS-CoV-2 antibodies (anti-SARS-CoV-2 electrochemiluminescence immunoassay/ECLIA) was used to assess the prevalence of SARS-CoV-2 infection in Lebanon. Results: In total, 13 755 participants were recruited over a 6-month period. Of these, 3168 (23.03%) individuals tested positive for anti-SARS-CoV-2, with levels of positivity varying among districts. A higher level of seropositivity was detected in the female participants. Conclusion: Seroprevalence against SARS-CoV-2 varied within Lebanon, but was comparable to the levels reported in the MENA region at the time of the study. The seroprevalence documented in this study represents a level of immunity that is not protective at the national level. Funding: This study was funded by the Lebanese American University School of Medicine.

Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study.

BACKGROUND: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population. METHODS: A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation. RESULTS: 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation. CONCLUSION: The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

SARS-CoV-2 Variants in Lebanon: Evolution and Current Situation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seen a worldwide spread since its emergence in 2019, including to Lebanon, where 534,968 confirmed cases (8% of the population) and 7569 deaths have been reported as of 14 May 2021. With the genome sequencing of strains from various countries, several classification systems were established via genome comparison. For instance, the GISAID clades classification highlights key mutations in the encoded proteins that could potentially affect the virus' infectivity and transmission rates. In this study, 58 genomes of Lebanese SARS-CoV-2 strains were analyzed, 28 of which were sequenced for this study, and 30 retrieved from the GISAID and GenBank databases. We aimed to classify these strains, establish their phylogenetic relationships, and extract the mutations causing amino acid substitutions within, particularly, the structural proteins. The sequenced Lebanese SARS-COV-2 strains were classified into four GISAID clades and 11 Pango lineages. Moreover, 21 uncommon mutations in the structural proteins were found in the newly sequenced strains, underlining interesting combinations of mutations in the spike proteins. Hence, this study constitutes an observation and description of the current SARS-CoV-2 genetic and clade situation in Lebanon according to the available sequenced strains.