Highlights d The receptor-binding motif (RBM) is a highly variable region of SARS-CoV-2 spike d RBM mutation N439K has emerged independently in multiple lineages d N439K increases spike affinity for hACE2; viral fitness and disease are unchanged d N439K confers resistance to several mAbs and escapes some polyclonal responses

Background Coronavirus disease 2019 (COVID-19) has been associated to microvascular alterations. We screened the fundus of patients with COVID-19 to detect alterations of the retina and its vasculature and to assess possible correlations with clinical parameters. Methods Cross-sectional study. The presence of retinal alterations in patients with COVID-19 and subjects unexposed to the virus was assessed using fundus photographs and their prevalence was compared. Mean arteries diameter (MAD) and mean veins diameter (MVD) were compared between patients and unexposed subjects with multiple linear regression including age, sex, ethnicity, body mass index, smoking/alcohol consumption, hypertension, hyperlipidaemia, diabetes as covariates. The influence of clinical/lab parameters on retinal findings was tested in COVID-19 patients. Findings 54 patients and 133 unexposed subjects were enrolled. Retinal findings in COVID-19 included: haemorrhages (9·25%), cotton wools spots (7·4%), dilated veins (27·7%), tortuous vessels (12·9%). Both MAD and MVD were higher in COVID-19 patients compared to unexposed subjects (98·3 ± 15·3 µm vs 91·9 ± 11·7 µm, p = 0.006 and 138·5 ± 21·5 µm vs 123·2 ± 13·0 µm, p <0.0001, respectively). In multiple regression accounting for covariates MVD was positively associated with COVID-19 both in severe (coefficient 30·3, CI95% 18·1–42·4) and non-severe (coefficient 10·3, CI95% 1·6–19·0) cases compared to unexposed subjects. In COVID-19 patients MVD was negatively correlated with the time from symptoms onset (coefficient −1·0, CI 95% −1·89 to −0·20) and positively correlated with disease severity (coefficient 22·0, CI 95% 5·2–38·9). Interpretation COVID-19 can affect the retina. Retinal veins diameter seems directly correlated with the disease severity. Its assessment could have possible applications in the management of COVID-19. Funding None.

The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February-19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6 %) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1 %) and their median age was 61 years (IQR 50-72). The timedependent probability of death was 19.7 % (95 % CI 14.6-24.9 %) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95 % CI 1.48−2.92 per ten years more) and obesity (aHR 3.04, 95 % CI 1.42−6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95 % CI 1.41−48.29), C-reactive protein levels (aHR 1.17, 95 % CI 1.02−1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95 % CI 1.37−4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20 %. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.