Background: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression. Methods: We established a medical surveillance team monitoring 63 geriatric institutions. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied. Results: After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 21/39(54%) pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died(median day 13.5,IQR 12). Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as a risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027). On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012). No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2 nucleocapsid protein). Conclusions: In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection.

Background: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression. Methods: We established a medical surveillance team monitoring 63 geriatric institutions in Buenos Aires, Argentina during June-July 2020. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied. Results: After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 54% of pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died. Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027). On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012). No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2). Conclusions: In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection.

Background: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression. Methods:We established a medical surveillance team monitoring 63 geriatric institutions. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied. Results:After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 21/39(54%) pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died(median day 13.5,IQR 12). Open Peer Review Reviewer Status AWAITING PEER REVIEWAny reports and responses or comments on the article can be found at the end of the article. Gates

No abstract

Metformin monotherapy is often insufficient to achieve or sustain glycemic targets in people with type 2 diabetes. Therefore, we performed a systematic review and meta-analysis to assess the efficacy, safety and tolerability of sodium-glucose co-transporter-2 inhibitors versus placebo as add-on therapy after metformin in type 2 diabetes. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search was performed in the PubMed, www.clinicaltrials.gov and Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials up until 30th October 2020 that compared sodium-glucose co-transporter-2 inhibitors versus placebo as add-on therapy to metformin. A random-effects model was used. Thirteen randomized controlled trials (4270 participants) met the inclusion criteria. Compared with placebo, sodium-glucose co-transporter-2 inhibitor treatment, as add-on therapy to metformin, was associated with a significant reduction in HbA1c level (mean difference [MD]: -0.6%, 95% CI: -0.7, -0.5; p<0.01), fasting plasma glucose level (MD: -1.4mmol/l; 95% CI; -1.5, -1.3; p<0.01), weight (MD: -2.0kg; 95% CI: -2.2, -1.8; p<0.01), systolic blood pressure (MD: -4.7mmHg; 95% Cl: -5.4, -3.9; p<0.01) and diastolic blood pressure (MD: -2.0mmHg; 95% Cl: -2.5, -1.5; p<0.01). Significantly more participants achieved HbA1c <7% (odds ratio [OR]: 3.1; 95% CI: 2.6, 3.6; p<0.01) in the sodium-glucose co-transporter-2 inhibitor group. Genital mycotic infections (OR: 2.6; 95% CI: 1.4, 4.6; p<0.01) were more common with sodium-glucose co-transporter-2 inhibitors, but there was no significant statistical difference in urinary tract infections (OR: 1.4; 95% CI: 1.0, 2.0; p=0.06), in hypoglycemia (OR: 1.5; 95% CI: 1.0, 2.4; p=0.07), or in discontinuation rates due to adverse events (OR: 0.9; 95% CI: 0.6, 1.5; p=0.68) between the two groups. In summary, in comparison with placebo, add-on therapy with a sodium-glucose co-transporter-2 inhibitor is significantly more efficacious in lowering HbA1c, fasting plasma glucose, weight and blood pressure in people with type 2 diabetes following inadequate glycemic control with metformin. The rate of discontinuation due to adverse events was similar despite higher risk of genital mycotic infections.