FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection (preprint)

Host metabolic fitness is a critical determinant of infectious disease outcomes. In COVID-19, obesity and aging are major high-risk disease modifiers, although the underlying mechanism remains unknown. Here, we demonstrate that fatty acid binding protein 4 (FABP4), a critical regulator of metabolic dysfunction in these conditions, regulates SARS-CoV2 pathogenesis. Our study revealed that elevated FABP4 levels in COVID-19 patients strongly correlate with disease severity. In adipocytes and airway epithelial cells we found that loss of FABP4 function by genetic or pharmacological means impaired SARS-CoV2 replication and disrupted the formation of viral replication organelles. Furthermore, treatment of infected hamsters with FABP4 inhibitors alleviated lung damage and fibrosis and reduced lung viral titers. These results highlight a novel host factor critical for SARS-CoV2 infection and the therapeutic potential of FABP4-targeting agents in treating COVID-19 patients.

Alterations in Vaginal Microbiota among Pregnant Women with COVID-19 (preprint)

Objective: To describe the alterations of the composition of vaginal microbiota in pregnant women with COVID-19. Design: Prospective observational single-centre study Setting: Tertiary referral hospital Participants: Pregnant women with COVID-19 Methods: The vaginal swabs were collected during the active phase of infection and consecutively, within a month after recovering from infection. In three patients, longitudinal samples before, in the course, and after infection were also obtained. The microbiome alterations were examined by 16S rRNA gene sequencing. Main outcome measures: Vaginal microbiota profiles in pregnant women with COVID-19 Results: Nineteen pregnant women with COVID-19 and 28 healthy controls who were matched according to the maternal age and gestational week were recruited. Shannon index and inverse Simpson index for cross-sectional cohort indicate that alpha diversity is significantly higher in women with COVID-19 (P=0.007 and P=0.006, respectively). There was a significantly decrease in Firmicutes (P=0.007) and Lactobacillus (P=0.019) with an increase in Bacteroidetes (P=0.024) in women with COVID-19 when compared to those of healthy controls. The higher amounts of Ureaplasma were found in women with the moderate/severe disease, compared to those of the asymptomatic/mild disease (P=0.001). Lactobacillus gasseri disappeared in women with the moderate/severe disease. Prevotella timonensis was identified only in the COVID-19 group. In longitudinal analysis, Actinobacteria was elevated, Firmicutes and Bacteroides depleted during the active phase. Conclusion: The study revealed that vaginal dysbiosis with a low abundance of Lactobacillus and an increase in Bacteroidetes is associated with COVID-19.

Immunogenicity of BNT162b2 and CoronaVac boosters in fully vaccinated individuals with CoronaVac against SARS-CoV-2: A Longitudinal Study (preprint)

Objective: There is a need for the immunogenicity of different boosters after widely used inactivated vaccine regimens. We aimed to determine the effects of BNT162b2 and CoronaVac boosters on the humoral and cellular immunity of individuals who had two doses of CoronaVac vaccination. Methods: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul. Individuals who had two doses of CoronaVac and no history of COVID-19 were included. The baseline blood samples were collected three to five months after two doses of CoronaVac. Follow-up samples were taken one and three months after third doses of CoronaVac or one dose of mRNA BNT162b2 boosters. Neutralizing antibody titers were detected by plaque reduction assay. T cell responses were evaluated by Elispot assay and flow cytometry. Results: We found a 3.38-fold increase in neutralizing antibody titers (Geometric Mean Titer [GMT], 78.69) one month after BNT162b2 booster and maintained at the three months (GMT, 80). However, in the CoronaVac group, significantly lower GMTs than BNT162b2 after 1 month and 3 months (21.44 and 28.44, respectively) indicated the weak immunogenicity of the CoronaVac booster (p<0.001). In the ELISpot assay, IL-2 levels after BNT162b2 were higher than baseline and CoronaVac booster (p<0.001) and IFN-γ levels were significantly higher than baseline (P<0.001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated significantly at the 3 month of the BNT162b2 boosters. Conclusion: The neutralizing antibody levels after three months of the BNT162b2 booster were higher than the antibody levels after CoronaVac. On the other hand, specific T cells might contribute to immune protection. By considering the waning immunity, we suggest a new booster dose with BNT162b2 for the countries that already have two doses of primary CoronaVac regimens.

Alterations in Vaginal Microbiota among Pregnant Women with COVID-19 (preprint)

Background: The maintenance of vaginal microbiota is an important factor to achieve ideal pregnancy outcomes. Coronavirus disease (COVID-19) has been shown to have potential adverse effects on pregnancy and neonatal outcomes. Pregnancy itself is a risk factor for the severity of COVID-19, with an increased risk of intensive care unit (ICU) admission, maternal morbidity, and mortality. the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in vaginal microbiome composition in pregnant women with COVID-19 has not yet been investigated. Therefore, we anticipate that COVID-19 may unfavorably affect the composition of the vaginal microbiota, resulting in adverse pregnancy outcomes. We aimed to describe the alterations of the composition of vaginal microbiota in pregnant women with COVID-19.Results: A prospective case-control study was conducted among 19 pregnant women with COVID-19 and 28 healthy controls matched according to the gestational week and age. The vaginal swabs were collected during the active phase of infection and consecutively, within a month after recovering from infection. In three patients, longitudinal samples before, in the course, and after infection were also obtained. The microbiome alterations were examined by 16S rRNA gene sequencing. We indicated that COVID-19 was associated with vaginal dysbiosis during pregnancy, which was indicated by an increased alpha diversity index. There was a significantly decrease in Firmicutes (P=0.007) and Lactobacillus (P=0.019) with an increase in Bacteroidetes (P=0.024) in the COVID-19 group. In the moderate/severe group, increased amounts of Ureaplasma and vanishing of Lactobacillus gasseri were found in women, compared to the asymptomatic or mild group (P=0.001). In longitudinal analysis, elevation of Actinobacteria with reduction of Firmicutes and Bacteroides were indicated during the active phase. Conclusions: The study revealed vaginal dysbiosis with a low abundance of Lactobacillus and an increase in Bacteroidetes in relation to SARS-CoV-2 infection. Vaginal dysbiosis in COVID-19 could be a contributing factor in pregnancy adverse outcomes. Trial registration: clinicaltrials, Registered 15 November 2019, https://www.clinicaltrials.gov/ct2/show/NCT04165252?cond=microbiota&cntry=TR&draw=3&rank=12

Machine learning detects SARS-CoV-2 and variants rapidly on DNA aptamer metasurfaces (preprint)

COVID-19 is detected using reverse transcription polymerase chain reaction (RT-PCR) of nasal swabs. A very sensitive and rapid detection technique using easily-collected fluids like saliva must be developed for safe and precise mass testing. Here, we introduce a metasurface platform for direct sensing of COVID-19 from unprocessed saliva. We computationally screen gold metasurfaces out of a pattern space of 2100 combinations for strongly-enhanced light-virus interaction with machine learning and use it to investigate the presence and concentration of the SARS-CoV-2. We use machine learning to identify the virus from Raman spectra with 95.2% sensitivity and specificity on 36 PCR positive and 33 negative clinical samples and to distinguish wild-type, alpha, and beta variants. Our results could pave the way for effective, safe and quantitative preventive screening and identification of variants.

Predictors of SARS CoV-2 Infection Among Healthcare Workers: The Impact of Community-Hospital Gradient (preprint)

Aim: We aimed to detect the risk factors for SARS-CoV-2 infection among healthcare workers (HCWs) in 2020, before vaccination era. Methods: We surveyed the SARS-CoV-2 infection among the HCWs in a hospital by screening of antibody levels and detection of viral RNA by reverse transcription polymerase chain reaction (RT-PCR) between May 2020 to December 2020. Occupational and non-occupational potential predictors of disease were surveyed for the HCWs included in this study. Results: Among 1925 personnel in the hospital, 1732 were included to the study with the response rate of 90%. Overall seroprevalence was 15% at the end of 2020, before vaccinations started. In multivariate analysis, being janitorial staff (OR:2.24, CI:1.21-4.14, p=0.011), being medical secretary (OR: 4.17, CI: 2.12-8.18, p<0.001), having at least one household member with COVID-19 diagnosis (OR:8.98, CI: 6.64-12.15, p<0.001) and number of household members >3 (OR:1.67, CI:1.26-2.22, p<0.001) were found to be significantly associated with SARS-CoV-2 infection. Conclusion: By the end of 2020, just before the era of vaccination and variants, seroprevalence was 15% among HCWs. Medical secretary and janitorial staff were under increased risk of SARS-CoV-2 infection. Community-hospital gradient can explain the mode of transmission for infection among HCWs. In the setting of this study, community measures were less strict, whereas hospital infection control was adequate and provided necessary personal protective equipment. Increasing risk in larger households and households with diagnosed COVID-19 patient indicates community acquired transmission of the infection.

Infectivity of Adult and Pediatric COVID-19 Patients (preprint)

We report infectivity of adult and pediatric COVID-19 patients in presence of  viral shedding and anti-SARS-CoV-2  antibody response A total of 408 consequent samples from eleven adult and five pediatric patients with SARS-CoV-2 infection were included. The samples every second day from saliva, nasopharynx, feces, serum, urine, tear were studied by RT-PCR and viral culture. Anti-SARS-CoV-2 antibodies were measured. The median duration of RNA shedding in all specimens was 7(2-15) days in adults and 5(3-19) days in children. The median duration from onset of symptoms to admission was three days.The viral RNA was positive in 44.7 % of the nasopharynx and 37.6% of saliva samples up 16 days in adults and 19 days in chldren. The latest viral culture positivity was detected on day 8 of symptoms in nasopharynx. The viral RNA was found in 6.1% of feces, 4.4% ofserum, 4.3 % of tear, 2.9% of urine. The earliest seroconversion was the 7th day for adults and 8th day for children. Atthe 14th day, total antibody positivity was 78% in adults, and 80% in children. After seroconversion, the viral RNA was still detected in the nasopharynx and saliva of three patients, however, the infectious virus was not present. Earlier hospital admission could be associated with shorter SARS-CoV-2 RNA shedding. The infectivity of patient is very low after 8 days of symptoms. The risk of fecal-oral transmission is very low, and strict hand hygiene measures could be preventive. The positive antibody test result could be used as a discharge criterion. 

Prophylactic use of Hydroxychloroquine among Physicians working in Pandemic Hospitals (preprint)

Background: Throughout the pandemic, physicians working at the frontlines have embarked on various quests to protect themselves, and many physicians preferred the use of hydroxychloroquine (HQN) as a prophylactic agent. This study aimed to investigate the reasons leading physicians to use HQN and the effects of HQN use on physicians.Methods: This study is a cross-sectional study with a target population of physicians working in pandemic hospitals in İstanbul, Turkey. We have recruited the participants from seven different hospitals via an invitation email between May 14 and June 13, 2020. An online questionnaire, including 57 questions in total, was sent to each physician.Results: A total of 148 (26%) physicians used hydroxychloroquine for prevention. Older physicians and ones who have a story of exposure to COVID-19 patients without any protection used more prophylactic HQN. Hydroxychloroquine did not differ statistically in terms of being infected among the exposed physicians (p=0.52). Nineteen (13%) physicians using hydroxychloroquine developed side effects related to the drug. Diarrhea and nausea were the most common.Conclusion: Prophylactic HQN use was more common among the physicians older than 40 years and who had higher exposure rates to a COVID-19 patient without any protection. The physicians working at the frontlines had the highest rate of infection. Hydroxychloroquine was not effective in the prophylaxis of COVID-19 among the exposed physicians.

Molecular Communication Theoretical Modeling and Analysis of SARS-CoV2 Transmission in Human Respiratory System (preprint)

Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV2) caused the ongoing pandemic. This pandemic devastated the world by killing more than a million people, as of October 2020. It is imperative to understand the transmission dynamics of SARS-CoV2 so that novel and interdisciplinary prevention, diagnostic, and therapeutic techniques could be developed. In this work, we model and analyze the transmission of SARS-CoV2 through the human respiratory tract from a molecular communication perspective. We consider that virus diffusion occurs in the mucus layer so that the shape of the tract does not have a significant effect on the transmission. Hence, this model reduces the inherent complexity of the human respiratory system. We further provide the impulse response of SARS-CoV2-ACE2 receptor binding event to determine the proportion of the virus population reaching different regions of the respiratory tract. Our findings confirm the results in the experimental literature on higher mucus flow rate causing virus migration to the lower respiratory tract. These results are especially important to understand the effect of SARS-CoV2 on the different human populations at different ages who have different mucus flow rates and ACE2 receptor concentrations in the different regions of the respiratory tract.

What Can We Estimate from Fatality and Infectious Case Data using the Susceptible-Infected-Removed (SIR) model? A case Study of Covid-19 Pandemic (preprint)

The rapidly spreading Covid-19 that affected almost all countries, was first reported at the end of 2019. As a consequence of its highly infectious nature, countries all over the world have imposed extremely strict measures to control its spread. Since the earliest stages of this major pandemic, academics have done a huge amount of research in order to understand the disease, develop medication, vaccines and tests, and model its spread. Among these studies, a great deal of effort has been invested in the estimation of epidemic parameters in the early stage, for the countries affected by Covid-19, hence to predict the course of the epidemic but the variability of the controls over the course of the epidemic complicated the modeling processes. In this article, the determination of the basic reproduction number, the mean duration of the infectious period, the estimation of the timing of the peak of the epidemic wave is discussed using early phase data. Daily case reports and daily fatalities for ten countries over the period January 22, 2020 - April 18, 2020 are evaluated using the Susceptible-Infected-Removed (SIR) model. For each country, the SIR models fitting cumulative infective case data within 5% error are analysed. It is observed that the basic reproduction number and the mean duration of the infectious period can be estimated only in cases where the spread of the epidemic is over (for China and South Korea in the present case). Nevertheless, it is shown that the timing of the maximum and timings of the inflection points of the proportion of infected individuals can be robustly estimated from the normalized data. The validation of the estimates by comparing the predictions with actual data has shown that the predictions were realised for all countries except USA, as long as lock-down measures were retained.