Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent COVID-19: A Prospective Observational Cohort Study.

BACKGROUND: There is a need to understand the duration of infectivity of primary and recurrent coronavirus disease 2019 (COVID-19) and identify predictors of loss of infectivity. METHODS: Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US Centers for Disease Control and Prevention (CDC) criteria (fever resolution, symptom improvement, and negative RADT) to predict loss of infectivity was also investigated. RESULTS: In total, 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n = 107, 88.4%) had received ≥3 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 odds ratio [OR], 0.14; P < .001]; day 7 OR, 0.04; P = .003]) and were all non-infective by day 10 (P = .02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; P = .003), an RT-PCR cycle threshold [Ct] value <23 (aOR on day 5, 22.75; P < .001) but not symptom improvement or RADT result.The CDC criteria would identify 36% (24/67) of all non-infectious individuals on day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. CONCLUSIONS: Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.

Characteristics and outcomes of family-practice patients with coronavirus disease 2019: a case series.

BACKGROUND: The clinical history and outcomes of coronavirus disease 2019 among people not hospitalized is not yet well characterized. To better inform clinical evaluation, we set out to characterize the natural history of coronavirus disease 2019 in primary health care. METHODS: Case series of all patients rostered to physicians at a university-affiliated Family Medicine clinic. Cases met the Centers for Disease Control and Prevention definition of coronavirus disease 2019 from March 1 to May 21 2020. RESULTS: In total, 89 patients meeting Centers for Disease Control and Prevention criteria for coronavirus disease 2019 were documented. Their average age was 55.6 years (range 6-95 years), and all but one was symptomatic. Fifty-seven cases (64%) had a polymerase chain reaction test for coronavirus disease 2019, of whom 77.2% tested positive. Thirty cases (33.7%) reported contact with a confirmed or probable case of coronavirus disease 2019. Based on the Charlson Comorbidity Index, 28 cases (31.5%) had no comorbid conditions. The median number of days from symptom onset to first polymerase chain reaction test was 6 days (interquartile range 2.3-11 days). The median duration of fever was 3.5 days (interquartile range 1-7 days). Twenty-four cases (27%) visited the Emergency Department, and 10 were admitted to hospital. The median number of days between symptom onset and first Emergency Department visit was 8 days (interquartile range 3.5-27 days). CONCLUSIONS: At the start of this pandemic, the implementation of basic measures such as diagnostic testing was delayed. If we are to improve our control over the spread of coronavirus disease 2019, we will need to substantially reduce the time from symptom onset to diagnostic testing, and subsequent contact tracing. To minimize unnecessary Emergency Department visits, we propose a testable strategy for Family Medicine to engage with coronavirus disease 2019 patients in the acute phase of their illness.

Covid-19 vaccine acceptance, hesitancy, and refusal among Canadian healthcare workers: A multicenter survey.

BACKGROUND: Determinants of COVID-19 vaccine acceptance among healthcare workers (HCW) remains poorly understood. We assessed HCWs' willingness to be vaccinated and reasons underlying hesitancy. METHODS: Cross-sectional survey across 17 healthcare institutions. HCWs eligible for vaccination (Pfizer-BioNTech mRNA) in December 2020 were invited to receive immunization. Multivariate logistic regression was performed to identify predictors of acceptance. Reasons for refusal among those who never intended to be vaccinated (ie, firm refusers) and those who preferred delaying vaccination (ie, vaccine hesitants) were assessed. RESULTS: Among 2,761 respondents (72% female, average age, 44), 2,233 (80.9%) accepted the vaccine. Physicians, environmental services workers and healthcare managers were more likely to accept vaccination compared to nurses. Male sex, age over 50, rehabilitation center workers, and occupational COVID-19 exposure were independently associated with vaccine acceptance by multivariate analysis. Factors for refusal included vaccine novelty, wanting others to receive it first, and insufficient time for decision-making. Among those who declined, 74% reported they may accept future vaccination. Vaccine firm refusers were more likely than vaccine hesitants to distrust pharmaceutical companies and to prefer developing a natural immunity by getting COVID-19. CONCLUSIONS: Vaccine hesitancy exists among HCWs. Our findings provide useful information to plan future interventions and improve acceptance.

Augmented quantal release of acetylcholine at the vertebrate neuromuscular junction following tdp-43 depletion.

TAR DNA binding protein (TDP-43) is a 43 kD, predominately nuclear, protein involved in RNA metabolism. Of clinical significance is that the majority of amyotrophic lateral sclerosis (ALS) patients display abnormal accumulation of misfolded TDP-43 in the cytoplasm, which is coincident with a loss of nuclear localization in the afflicted regions of the central nervous system. Little is known about defects that arise in loss-of-function models, in particular synaptic defects that arise at the neuromuscular junction (NMJ). In this report, we examined abnormalities arising at the NMJ following depletion of tdp-43 using a previously characterized mutant tardbp (encoding tdp-43) zebrafish line containing a premature stop codon (Y220X) that results in an unstable and degraded protein. Homozygous tardbpY220X/Y220X zebrafish do not produce tdp-43 but develop normally due to expression of an alternative splice variant of tardbpl (tardbp paralog). Using an antisense morpholino oligonucleotide to knockdown expression of the tardbpl in tardbpY220X/Y220X embryos, we examined locomotor defects, NMJ structural abnormalities and release of quantal synaptic vesicles at the NMJ. As in previous reports, larvae depleted of tdp-43 display reduced survival, gross morphological defects and severely impaired locomotor activity. These larvae also displayed an increased number of orphaned pre- and postsynaptic NMJ markers but surprisingly, we observed a significant increase (3.5 times) in the frequency of quantal acetylcholine release at the NMJ in larvae depleted of tdp-43. These results indicate that reduced TDP-43 levels alter quantal vesicle release at the NMJ during vertebrate development and may be relevant for understanding synaptic dysfunction in ALS.

The larvicide pyriproxyfen blamed during the Zika virus outbreak does not cause microcephaly in zebrafish embryos.

Although the zika virus (ZIKV) has now been strongly correlated with emerging cases of microcephaly in the Americas, suspicions have been raised regarding the use of pyriproxyfen, a larvicide that prevents mosquito development, in drinking water. The effects of this compound on neurodevelopment have not yet been addressed specifically in vertebrates. As a result, we aimed at addressing the effects, if any, of pyriproxyfen on neurodevelopment in the zebrafish embryo as a vertebrate model. Using zebrafish transgenic lines expressing GFP in different cell populations (elavl3 in newborn neurons, gfap and nestin in neural stem cells), we focused on the analysis of whole embryonic brain volume after confocal 3D-reconstruction and the quantification of purified neural stem cells during early neurodevelopment by FACS-cell sorting from whole in vivo embryos. Interestingly, though lethal at very high doses, pyriproxyfen did not cause brain malformation nor any significant changes in the number of observed stem cells in the developing central nervous system. Our data indicate that pyriproxyfen does not affect central nervous system development in zebrafish, suggesting that this larvicide on its own, may not be correlated with the increase in microcephaly cases reported recently.