Asymptomatic COVID-19 in the elderly: dementia and viral clearance as risk factors for disease progression.

Abstract

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.

Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19

“…In this trial, 75% of participants received advanced respiratory support, which often occurs between 7 days and 10 days after symptom onset, and by which stage in the disease many patients who are immunocompetent will have developed endogenous antibody responses. 22 This could explain the overall results, including the effect observed in the prespecified immunodeficiency subgroup (Figure 4). Organ support-free days A, The ordinal scale includes death (in-hospital death, the worst possible outcome) and a score of 0 to 21 (the numbers of days alive without organ support) by trial group as the cumulative proportion (y-axis) for each trial group by day (x-axis), with death listed first.…”

“…For the convalescent plasma group, the median WHO score was 6 (required intubation and mechanical ventilation) and the IQR range was 3 (hospitalized but did not require oxygen therapy) to 7 (required ventilation plus additional organ support with vasopressors, kidney replacement therapy, or ECMO). For the no convalescent plasma group, the median WHO score was 5 (required noninvasive mechanical ventilation or high-flow oxygen) and the IQR was the combined 0- These findings also warrant further investigation of the hypotheses that benefit with convalescent plasma may be different early on in the illness, 22,23 and perhaps in patients with an impaired immune system who are unable to mount effective immune responses, including antibody responses. 23,24 The prespecified anti-SARS-CoV-2 antibody and SARS-CoV-2 polymerase chain reaction status subgroups were used to evaluate the hypotheses that the antibody-negative population and respiratory polymerase chain reaction-positive population may derive benefit from convalescent plasma therapy.…”

Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19

“…A total of 4357 records were identified in databases, registries, and other sources. There were 4 RCTs published in peer-reviewed journals [16][17][18][19] and 5 RCTs published as preprints [20][21][22][23][24] that were included. In addition, press releases were identified for 2 RCTs (the RECOVERY trial 8 and the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia [REMAP-CAP] 25 ) but only the reported results from the RECOVERY trial 8 (NCT04381936) were included, stating 1873 deaths among 10 406 patients randomized (eFigure 1 in the Supplement).…”

“…The observations reported in the literature regarding a benefit with early high-titer plasma 1 administration in observational studies call for further analyses based on individual patient data such as the Continuous Monitoring of Pooled International Trials of Convalescent Plasma for COVID-19 Hospitalized Patients (COMPILE) project. 30 Fourth, except for 1 RCT with outpatients, 16 all patients were hospitalized with or without oxygen supplementation, indicative of moderate to critical COVID-19. The generalizability of the results to patients with milder COVID-19 is unclear.…”