The effect of post-COVID-19 on gustatory and olfactory function: A preliminary case-controlled study.

AIMS: The aim of the study was to analyze objective and subjective olfactory/gustatory function in post-COVID-19 infection (PCI). MATERIALS AND METHODS: Patients with past PCR-confirmed COVID-19 infection and persistent olfactory/gustatory complaints were investigated. Olfactory threshold and identification, gustatory detection, identification, and magnitude scaling were tested. RESULTS: A total of 42 PCI subjects were compared to 41 age- and gender-matched controls with no COVID-19 history. All PCI tested had mild COVID-19 disease. Mean interval between COVID-19 confirmations to testing was 7.4 ± 3.1 months. PCI subjects complained of combined dysfunction in 85.7%, isolated olfactory or gustatory dysfunction in 7.1% each. Combined complaints were significantly higher in PCI (p < 0.001). Objective testing showed significantly higher prevalence of dysfunction in PCI versus controls for hyposmia (73.8%, 12.2%), anosmia (11.9%, 0%), odor identification (68.5%, 83.0%), hypogeusia (23% and 2.4%, respectively), and impaired magnitude scaling, (p < 0.05). All PCI subjects with hypogeusia had abnormal gustatory magnitude scaling. CONCLUSIONS: While most PCI subjects complained of combined gustatory and olfactory dysfunction, objective testing showed in the majority an isolated single sense dysfunction, with a low level of agreement between subjective and objective findings. Abnormal objective results for all olfactory and gustatory functions tested may suggest a central rather than peripheral mechanism, although concomitant mechanisms cannot be excluded.

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals, a prospective longitudinal cohort study.

PURPOSE: As protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion. METHODS: A prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster. RESULTS: Among 110 participants,56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25-11.67) folds and 2.40 (95 %CI 1.90-3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5-79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1-34.7) fold in and immunocompetent group, was observed. CONCLUSION: A third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.

ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern.

COVID-19, an infectious disease caused by the SARS-CoV-2 virus, emerged globally in early 2020 and has remained a serious public health issue. To date, although several preventative vaccines have been approved by FDA and EMA, vaccinated individuals increasingly suffer from breakthrough infections. Therapeutic antibodies may provide an alternative strategy to neutralize viral infection and treat serious cases; however, the clinical data and our experiments show that some FDA-approved monoclonal antibodies lose function against COVID-19 variants such as Omicron. Therefore, in this study, we present a novel therapeutic agent, SI-F019, an ACE2-Fc fusion protein whose neutralization efficiency is not compromised, but actually strengthened, by the mutations of dominant variants including Omicron. Comprehensive biophysical analyses revealed the mechanism of increased inhibition to be enhanced interaction of SI-F019 with all the tested spike variants, in contrast to monoclonal antibodies which tended to show weaker binding to some variants. The results imply that SI-F019 may be a broadly useful agent for treatment of COVID-19.

Immediate side effects of Comirnaty COVID-19 vaccine: A nationwide survey of vaccinated people in Israel, December 2020 to March 2021.

BackgroundCOVID-19 vaccine safety is of major interest worldwide, since there is no prior experience with it. Israel was one of the first countries to widely use the Comirnaty vaccine.AimWe aimed to assess the vaccine's short-term side effects directly from a large population and to predict influencing factors for self-reporting side effects.MethodsIn a retrospective cohort study, we investigated self-reported systemic vaccine side-effects using electronic surveys sent to vaccinated individuals between 20 December 2020 and 11 March 2021, within 3 days following administration of the first and second dose. We determined predictors for reporting systemic side effects by logistic regression.ResultsA total of 1,213,693 patients received at least one vaccine dose and 301,537 (24.8%) answered at least one survey. Among them, 68,162 (30.4%) and 89,854 (59.9%) individuals filled the first and the second dose surveys, respectively, and reported one or more side effects. Most common side effects were fatigue, headache and myalgia. Several respondents reported facial paraesthesia after first and second dose, respectively (n = 1,675; 0.7% and n = 1,601; 1.1%). Individuals younger than 40 years and women reported side effects more frequently than others, but pregnant women reported less. Pregnancy was a weak predictor for reporting any side effect in general and in particular fatigue, myalgia, headache, chills and fever.ConclusionsWe found further support for minor short-term side effects, within 3 days of receiving the Comirnaty vaccine. These findings from vaccine recipients in general and pregnant women in particular can improve vaccine acceptance.

ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern

COVID-19, an infectious disease caused by the SARS-CoV-2 virus, emerged globally in early 2020 and has remained a serious public health issue. To date, although several preventative vaccines have been approved by FDA and EMA, vaccinated individuals increasingly suffer from breakthrough infections. Therapeutic antibodies may provide an alternative strategy to neutralize viral infection and treat serious cases;however, the clinical data and our experiments show that some FDA-approved monoclonal antibodies lose function against COVID-19 variants such as Omicron. Therefore, in this study, we present a novel therapeutic agent, SI–F019, an ACE2-Fc fusion protein whose neutralization efficiency is not compromised, but actually strengthened, by the mutations of dominant variants including Omicron. Comprehensive biophysical analyses revealed the mechanism of increased inhibition to be enhanced interaction of SI–F019 with all the tested spike variants, in contrast to monoclonal antibodies which tended to show weaker binding to some variants. The results imply that SI–F019 may be a broadly useful agent for treatment of COVID-19. Graphical Image 1

Reactogenicity of a third BNT162b2 mRNA COVID-19 vaccine among immunocompromised individuals and seniors - A nationwide survey.

BACKGROUND: Since July 13, 2021, a third SARS-CoV-2 vaccine BNT162b2 was approved in Israel to immunocompromised and seniors 60 years of age or older. We aimed to evaluate vaccine's reactogenicity. METHODS: A retrospective cohort, using electronic surveys sent to booster vaccine recipients, during July 20-August 10, 2021. RESULTS: 17,820 participated in the survey, with a response rate of 30.2%. 3195 (17.9%) were immunocompromised. Fatigue, myalgia and fever were the most frequent systemic side effects reported (19.6%, 9.2% and 8.1% respectively among immunocompromised; 21.3%, 9.9% and 9.2% respectively among seniors). 67.3% of immunocompromised and 62% of seniors reported experiencing a better or a similar response to the third dose, compared to the second. CONCLUSIONS: Local and systemic reactions after third BNT162b2 vaccine, reported by immunocompromised and seniors, were similar to those observed following previous vaccines and mostly self-resolved. These findings may aid promoting confidence among vaccine providers and recipients.

COVID-19 in children and the effect of schools reopening on potential transmission to household members.

AIM: The effect of reopening schools on children's contribution to SARS-CoV-2 transmission, especially within households, remains controversial. This study describes the clinical presentation of a large ambulatory COVID-19 paediatric cohort and evaluates the role of children in household transmission prior to and following school reopening. METHODS: A retrospective database cohort study was conducted in a large Health Maintenance Organization in Israel. Data of all paediatric, laboratory-confirmed Coronavirus cases between 28/2/2020 and 20/6/2020 were extracted. All cases were analysed for household contacts and primary cases within each family cluster. RESULTS: A total of 1,032 cases under 18 years old (median age 12 years) were included. Of these cases, 432 (41.9%) were asymptomatic; 122 (11.8%) cases acquired the infection at school, and 45 of them were part of two school clusters; 846 children had at least one positive household contact, in 498 family clusters, and among them, 293 primary cases were identified. Only 27 (9.2%) primary cases were under 18 years of age and six (2%) were below 10. The proportion of primary cases did not change after the re-opening of educational facilities. CONCLUSION: Children, particularly under 10 years of age, are less likely to be the vector for SARS-CoV-2 infection within household settings. Opening educational facilities did not change transmission dynamics.

COVID-19 community care in Israel-a nationwide cohort study from a large health maintenance organization.

BACKGROUND: Among the many medical challenges presented by the COVID-19 pandemic, management of the majority of patients in community outpatient settings is crucial. The aim of this study was to describe the characteristics and outcomes among confirmed COVID-19 cases who were managed at three settings: two outpatient settings and one inpatient. METHODS: A retrospective database cohort study was conducted in a large Israeli Health Maintenance Organization. All COVID-19 cases diagnosed between 28 February 2020 and 20 July 2020 were included. Cases in the community settings were managed through a nationwide remote monitoring center, using preliminary telehealth triage and 24/7 virtual care. Outcome parameters included hospital admission, disease severity, need for respiratory support and mortality. RESULTS: About 5448 cases, aged range 0-97 years, were enrolled; 88.7% were initially managed as outpatient either at home or in designated hotels, 3.1 and 2.1% of them, respectively, later required hospitalization. The main reason for hospitalization was dyspnea; 12 were diagnosed with severe disease; 56 patients (1.3%) died, five (0.1%) of whom were initially allocated to the outpatient settings. CONCLUSIONS: Care for appropriately selected COVID-19 patients in the community provides a safe and effective option. This can contribute to reducing the hospitalization burden, with no evidence of increased morbidity or mortality.