Pupillographic Analysis of COVID-19 Patients: Early and Late Results After Recovery (preprint)

Purpose: We aimed to investigate the short and long-term static and dynamic pupillary responses of patients recovered from coronavirus disease – 19 (COVID-19) by using quantitative infrared pupillography.  Methods: This study included patients who recovered from COVID-19 (Group 1) and age- and gender-matched controls (Group 2). A detailed ophthalmic examination was performed at one month and six months after the diagnosis of COVID-19. Photopic, mesopic, and scotopic pupil diameters (PDs) were measured by using a quantitative infrared pupillography which was integrated into Scheimpflug/Placido photography-based topography system. Pupil diameters at 0, 2nd, 4th and 6th seconds, and average pupil dilation speeds at 2nd, 4th, 6th and 8th seconds were recorded. Results: Eighty-six eyes of 86 patients (Group 1: n=42; Group 2: n=44) were included. While the mean photopic, mesopic and scotopic PDs were significantly larger in the COVID-19 group than the control group in the first month (p = 0.035, p = 0.017, p = 0.018, respectively), no statistically significant difference was found in the sixth month. Besides, average pupil dilation speeds and PDs at the 0, 2nd, 4th and 6th seconds were not statistically significantly different between the two groups in the first month and sixth month.   Conclusions: Pupil diameters were significantly larger in COVID-19 patients in all light intensities in the first month after COVID-19. However, pupillary dilation was transient, and no significant difference was found in the sixth month. We suggest that the transient pupillary dilation may be secondary to the autonomic nervous system dysfunction following COVID-19.

Characterization of tungiasis infection and morbidity in Kenya reveals increase in disease burden during COVID-19 school closures. (preprint)

Background: Tungiasis is a common but extremely neglected tropical skin disease caused by the sand flea Tunga penetrans. Female sand fleas penetrate the skin, particularly at the feet, and cause severe inflammation with pain and itching, acute and chronic morbidity. This study aimed to characterize disease burden in two highly affected regions in Kenya, to test the use of simple thermography to detect tungiasis-associated inflammation and to create a new two-level classification of disease severity that may be used for mapping, targeting, and monitoring interventions in future.  Methods: From February 2020 to April 2021, 3,532 pupils age 8-14 years were randomly selected in 35 public primary schools and examined for tungiasis and associated pathology. Of the infected pupils, 266 were randomly selected and their households visited. An additional 1,138 family members were examined. Infra-red thermography was used to assess inflammation. An all-pathology score was created combining the number of locations on the feet with acute and chronic pathologies and infra-red hotspots.  Results: Based on multilevel mixed effects logistic models, the odds of infection with tungiasis among school pupils was three times as high in Kwale than in Siaya (adjusted odds ratio (AOR)0.28, 95% CI 0.1-0.6); three times higher in males than in females (AOR2.9, 95%CI 2.2-3.7) and three times lower among pupils sleeping in a house with a concrete floor (AOR0.32,95%CI 0.24-0.44). The odds of finding an infected person among the household population during active school terms was approximately a half of that when schools were closed due to COVID-19 (AOR0.44, 95% CI 0.3-0.7). Infection intensity was positively correlated with inflammation (Spearman’s rho =0.68, p<0.001) and all-pathology score (rho 0.86, p<0.001). Based on the two-level classification, severe cases were associated with a threefold higher level of pain (OR2.99, 95% CI 2-4.4) and itching (OR3.31, 95% CI 2.2-4.9) than mild cases. Conclusions: Thermography was a valuable addition for assessing morbidity and the proposed two-level classification of disease severity clearly separated patients with mild and severe impacts. The burden of tungiasis severely increased during COVID-19 restrictions and reinforced that underlying risks are found in the home environment more than in school.

An Econometric Analysis of FDNY’s Systemwide EMS Dispatch, Response and Operational Performance During the 2020 Covid Lockdown Using a Negative Binomial Model With Multiple Fixed Effects (preprint)

A negative binomial longitudinal (panel) count model with multiple fixed effects in the presence of over-dispersion is used to estimate the heterogenity effects of emergency 911 incidents or call volume, year, day of the week, dispatcher-assigned medical emergency call type, priority rank, ambulance (DUAL, ALS, BLS) response and borough on average ambulance travel time. We use FDNY Emergency Dispatch Data for the periods March 20, 2019–June 13, 2019 and the corresponding lockdown period of March 20, 2020–June13, 2020 for a year over year econometric analysis. The model addresses the limitations of two-by-two contingency table analysis when there are more than two categorical variables by utilizing the underlying statistical properties of the Poisson distribution in a multivariate parametric approach by analyzing the simultaneous effects of several explanatory variables.When clustered standard errors are corrected for fixed effects and over-dispersion, we find that there was no significant statistical difference in the relationship between average travel time and call volume in the 2019 and 2020 periods. Wednesday is only day of the week that was most likely to increase travel response time. All medical emergencies showed significant declines in average travel response time at a p-value = .05, except for call types designated as allergy that was significant at p-value less than .07. Clinical priority rank 6 that required the use of BLS equipment and EMT crews used in non-medical emergencies and other cases had no statistical effect on travel time in the comparison. When compared to Manhattan, Brooklyn and Queens had no significant statistical effect on average travel response time.

Long-Term Outcomes of COVID-19 Survivors and an Exploratory Analysis of Factors Associated with Sequela-Free Survival of Patients Treated at Leishenshan Hospital in Wuhan, China (preprint)

Objective: To determine key factors associated with sequela-free survival of patients with COVID-19.Design: Retrospective–prospective observational study.Setting: Leishenshan Hospital in Wuhan, China.Participants: Patients with COVID-19 admitted at Leishenshan Hospital in Wuhan, China between 15 February 2020 and 1 April 2020 and discharged.Main Outcomes: MeasuresSequela-free survival is defined as having none of the long-term sequelae measured with the Activity of Daily Living (ADL) Scale, Modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI) and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the key factors of sequela-free survival.ResultsThe follow-up period for the 464 patients was 10 August to 30 September 2020. Of these, 424 patients completed the assessment of all scales. 30.2% (128 of 424) were categorised as sequela-free at follow-up. The most common sequelae were psychosocial problems (254 [57.7%]), respiratory function abnormality (149 [32.6%]) and cardiac function abnormality (98 [21.5%]). Risk factors associated with COVID-19 sequelae were anaemia on admission, longer duration from the onset of symptoms to admission and advanced age, whereas anti-anaemia treatment was a protective factor against sequelae. A haemoglobin level of <113 g/l for female patients or <92 g/l for male patients at admission discriminated a higher risk of any COVID-19 sequelae.Conclusions: Only one third COVID-19 survivors were sequela-free. Anaemia on admission, longer duration from the onset of symptoms to admission and advanced age were the risk factors of any long-term sequela. Anti-anaemia treatment was associated with beneficial outcomes in COVID-19 survivors.Funding: This study was funded by grants to DSS from the National Natural Science Foundation of China (Nos.81771133, 81970995) (DSD grants), Shanghai Shenkang Hospital Development Center Founding (SHDC12017X11), Renji Hospital Clinical Innovation Foundation (PYMDT-007), Shanghai municipal Education Commission-Gaofeng Clinical Medicine Support (20191903), State Key Laboratory of Neuroscience(SKLN－201803), the National Natural Science Foundation of China (No.81701358) (DH grants), the Shanghai Municipal Commission of Health and Family Planning Funding (20184Y0205) (CYC grants) and Renji Hospital founding (RJZZ18-019) (LLH grants).Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Research Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiaotong University (ethics committee approval No. KY2020-34).

Long-Term Outcomes and Sequelae for 464 COVID-19 Patients Discharged from Leishenshan Hospital in Wuhan, China (preprint)

Background: While coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, millions of COVID-19 patients have recovered and returned to their families and work, although the long-term outcomes remain unknown.Methods: This retrospective–prospective study analysed data for COVID-19 patients discharged from Leishenshan Hospital in Wuhan, China. Long-term outcomes were measured by Activity of Daily Living (ADL) Scale, Modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI), and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the risk factors of long-term outcomes.Findings: The follow-up period for the 464 patients was August 10–September 30, 2020. The most common sequelae were psychosocial problems (254 [57·7%]), respiratory function abnormality (149 [32·6%]), and cardiac function abnormality (98 [21·5%]). Rare sequelae were ADL disability (61 [13·3%]); pain (55 [12·5%]); feeding difficulties (54 [12·2%]); dysphonia (46 [10·4%]); and hyposmia (27 [6·1%]), as well as impairment in hearing (40 [9·1%]), vison (37 [8·4%]), swallowing (30 [6·8%]), and gustation (18 [4·1%]). Almost all patients (98·2%) had normal cognitive function. Risk factors associated with ADL disability were advanced age, intensive care unit (ICU) stay, and cancer, which were also associated with respiratory function abnormality. Risk factors associated with cardiac function abnormality were long hospital stay, cancer, and respiratory diseases. Advanced age, ICU stay, and nonischemic heart diseases were associated with psychosocial problems. Compared with female patients, male patients had decreased odds of declined respiratory, cardiac function, depression and anxiety, and pain.Interpretation: Nearly normal ADL, moderate cardiopulmonary function and psychosocial issues, and minor sensory abnormalities were observed in COVID-19 survivors. Advanced age, ICU stay, cancer, and female sex were adverse risk factors in long-term sequelae. These data provide a generalisable estimate of long-term outcomes for COVID-19.Trial Registration: This study was registered in the ClinicalTrial.gov database (NCT04508712).Funding: National Natural Science Foundation of China, Shanghai Shenkang Hospital Development Center, Shanghai municipal Education Commission, State Key Laboratoy of Neuroscience, and Renji Hospital.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Research Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiaotong University (Ethical Committee approval number: KY2020-34). Oral consent was acquired from patients or from their immediate family members in cases of communication disorder or death.

Retinal imaging study diagnoses a case of COVID-19 (preprint)

Background: Hyper-reflective lesions at the level of ganglion cell (GCL) and inner plexiform retinal layers (IPL) by Optical Coherence Tomography (OCT) and cotton wool spots in the examination of the eye fundus have recently been described as findings in patients with COVID-19 infection.Case report: We report a case of a 42-year-old male anesthetist who treated COVID patients during the previous five weeks and suddenly debuted with a temporal relative scotoma in his left eye (OS); three weeks before, he presented with ageusia for several days. Best corrected visual acuity was 20/20 for OS; no discromatopsy or afferent pupillary defect were present. Visual field was performed, with no significant findings associated to the focal loss of sensitivity referred by the patient. The anterior segment was unremarkable on slit lamp examination in both eyes. Fundus examination of the left eye showed no significant findings. A placoid, hyperreflective band at the level of GCL and IPL was visible in the temporal and nasal side of the fovea on OCT which spared the outer retina, at the time of diagnosis and at one month. A propharyngeal swab test for SARS-CoV-2 RNA, IgG and IgM ELISA determinations were performed. Real-time reverse-transcriptase polymerase chain reaction (RT‐PCR) was negative. ELISA testing and a third rapid antibody detection test performed 7 days after the onset of symptoms were positive.Conclusions: Ocular signs and symptoms in COVID cases are rarely reported, but may be underestimated, especially those that affect the retina and occur in asymptomatic or paucisymptomatic cases. We present the first case of diagnosis of COVID-19 based on retinal ophthalmic examination. 

SARS-CoV-2 infection in primary schools in northern France: A retrospective cohort study in an area of high transmission (preprint)

Background: The extent of SARS-CoV-2 transmission among pupils in primary schools and their families is unknown. Methods: Between 28-30 April 2020, a retrospective cohort study was conducted among pupils, their parents and relatives, and staff of primary schools exposed to SARS-CoV-2 in February and March 2020 in a city north of Paris, France. Participants completed a questionnaire that covered sociodemographic information and history of recent symptoms. A blood sample was tested for the presence of anti-SARS-CoV-2 antibodies using a flow-cytometry-based assay. Results: The infection attack rate (IAR) was 45/510 (8.8%), 3/42 (7.1%), 1/28 (3.6%), 76/641 (11.9%) and 14/119 (11.8%) among primary school pupils, teachers, non-teaching staff, parents, and relatives, respectively (P = 0.29). Prior to school closure on February 14, three SARS-CoV-2 infected pupils attended three separate schools with no secondary cases in the following 14 days among pupils, teachers and non-teaching staff of the same schools. Familial clustering of cases was documented by the high proportion of antibodies among parents and relatives of infected pupils (36/59 = 61.0% and 4/9 = 44.4%, respectively). In children, disease manifestations were mild, and 24/58 (41.4%) of infected children were asymptomatic. Interpretation: In young children, SARS-CoV-2 infection was largely mild or asymptomatic and there was no evidence of onwards transmission from children in the school setting.