Anti-spike IgG antibody kinetics following the second and third doses of BNT162b2 vaccine in nursing home residents.

BACKGROUND: Duration of post-vaccination protection against COVID-19 in nursing home (NH) residents is a critical issue. The objective of this study was to estimate the duration of the IgG(S) response to the mRNA BNT162b2 vaccine in NH residents with (COV-Yes) or without (COV-No) history of SARS-CoV-2 infection. METHODS: A 574 COV-Yes and COV-No NH residents were included in 2 cohorts: Main (n = 115, median age 87 years) or Confirmatory (n = 459, median age 89 years). IgG(S) quantification was carried out at three different time points following the BNT162b2 vaccine: three (1st) and seven (2nd) months after the 2nd dose, and 1 month after the 3rd dose (3rd quantification) in the Main cohort, and twice (2nd and 3rd) in the Confirmatory cohort. The seroneutralization capacity according to COVID-19 history was also measured in a subgroup of patients. RESULTS: Neutralization capacity was strongly correlated with IgG(S) levels (R2 :76%) without any difference between COV-Yes and COV-No groups for the same levels of IgG(S). After the 2nd dose, duration of the assumed robust protection (IgG(S) >264 BAU/ml) was two-fold higher in the COV-Yes vs. COV-No group: 12.60 (10.69-14.44) versus 5.76 (3.91-8.64) months, with this advantage mainly due to the higher IgG(S) titers after the 2nd dose and secondary to a slower decay over time. After the 3rd dose, duration of robust protection was estimated at 11.87 (9.88-14.87) (COV-Yes) and 8.95 (6.85-11.04) (COV-No) months. These results were similar in both cohorts. CONCLUSIONS AND RELEVANCE: In old subjects living in NH, history of SARS-CoV-2 infection provides a clear advantage in the magnitude and duration of high IgG(S) titers following the 2nd dose. Importantly, the 3rd dose induces a much more pronounced IgG(S) response than the 2nd dose in COV-No subjects, the effect of which should be able to ensure a prolonged protection against severe forms of COVID-19 in these subjects.

Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality.

BACKGROUND: Although older adults are at high risk for severe coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission, age is often used as a selection criterion in case of ICU beds scarcity. We sought to compare the proportion, clinical features and mortality between patients ≥70 years old and younger ICU patients with COVID-19. METHODS: All patients, consecutively admitted to our COVID ICU, where age was not used as an admission criterion, from March 2020 through April 2021, were included. Demographics, clinical and laboratory characteristics were recorded. Illness severity and Charlson comorbidity Index (CCI) were calculated. Patients≥70 years old were compared to youngers. RESULTS: Of 458 patients (68 [59-76] years, 70% males), 206 (45%) were ≥70 years old. Compared to younger, older patients had higher illness severity scores (APACHE II 18 [14-23] versus 12 [9-16], P<0.001, SOFA 8 [6-10] versus 6 [2-8], P<0.001, CCI 5 [4-6] versus 2 [1-3], P<0.001), increased need for mechanical ventilation (92% vs. 72%, P<0.001) and ICU mortality (74% versus. 29%, P<0.001). Age (HR: 1.045, CI: 1.02-1.07, P=0.001), CCI (HR: 1.135, CI: 1.037-1.243, P=0.006) and APACHE II (HR: 1.070, CI: 1.013-1.130, P=0.015) were independently associated with mortality. Among comorbidities, obesity, chronic pulmonary disease and chronic kidney disease were independent risk factors for death. CONCLUSIONS: When age is not used as criterion for admission to COVID ICU, patients ≥70 years old represent a considerable proportion and, compared to younger ones, they have higher mortality. Age, severity of illness and CCI, and certain comorbidities are independent risk factors for mortality.

Underrepresentation of older adults in clinical trials on COVID-19 vaccines: A systematic review.

During the COVID-19 pandemic older subjects have been disproportionately affected by the disease. Vaccination is a fundamental intervention to prevent the negative consequences of COVID-19, but it is not known if the needs and vulnerabilities of older people are adequately addressed by their inclusion in randomized clinical trials (RCTs) evaluating the efficacy of vaccines for COVID-19. Given this background, we aimed to evaluate if current and ongoing phase II-III RCTs evaluating the efficacy of COVID-19 vaccines included a representative sample of older people. A systematic literature search in PubMed and Clinicaltrials.gov was performed until May 01st, 2021. Among 474 abstracts initially retrieved, 20 RCTs (ten already published, ten ongoing) were included. In the ten studies already published, the mean age of participants was 45.2 ± 11.9 years and only 9.83% of the participants were more than 65 years, 1.66% more than 75 years and less than 1% (0.55%) more than 85 years. In the ten ongoing RCTs, many of the studies aimed at including participants older than 18 years, with one study including participants between 18 and 84 years, and two between 21 and 100 years. In conclusion, our systematic review demonstrates that in published and ongoing phase II-III randomized clinical trials evaluating the efficacy of COVID-19 vaccines only a tiny fraction of the most vulnerable group of older people was included, although they clearly were the first population that had to be vaccinated.

Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications.

PURPOSE: In the pathogenesis of severe COVID-19 complications, derangements of renin-angiotensin-aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases. METHODS: We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors. RESULTS: Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins. CONCLUSIONS: Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group.

The Nexus Between Telomere Length and Lymphocyte Count in Seniors Hospitalized With COVID-19.

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646.

August 2020 Interim EuGMS guidance to prepare European Long-Term Care Facilities for COVID-19.

PURPOSE: The European Geriatric Medicine Society (EuGMS) is launching a second interim guidance whose aim is to prevent the entrance and spread of COVID-19 into long-term care facilities (LTCFs). METHODS: The EuGMS gathered experts to propose a guide of measures to prevent COVID-19 outbreaks in LTCFs. It is based on the specific features of SARS-CoV-2 transmission in LTCFs, residents' needs, and on experiences conducted in the field. RESULTS: Asymptomatic COVID-19 residents and staff members contribute substantially to the dissemination of COVID-19 infection in LTCFs. An infection prevention and control focal point should be set up in every LTCF for (1) supervising infection prevention and control measures aimed at keeping COVID-19 out of LTCFs, (2) RT-PCR testing of residents, staff members, and visitors with COVID-19 symptoms, even atypical, and (3) isolating subjects either infected or in contact with infected subjects. When a first LCTF resident or staff member is infected, a facility-wide RT-PCR test-retest strategy should be implemented for detecting all SARS-CoV-2 carriers. Testing should continue until no new COVID-19 cases are identified. The isolation of residents should be limited as much as possible and associated with measures aiming at limiting its negative effects on their mental and somatic health status. CONCLUSIONS: An early recognition of symptoms compatible with COVID-19 may help to diagnose COVID-19 residents and staff more promptly. Subsequently, an earlier testing for SARS-CoV-2 symptomatic and asymptomatic LTCF staff and residents will enable the implementation of appropriate infection prevention and control. The negative effects of social isolation in residents should be limited as much as possible.

A Mechanism for Severity of Disease in Older Patients with COVID-19: The Nexus between Telomere Length and Lymphopenia.

BACKGROUND: Lymphopenia due to a plummeting T-cell count is a major feature of severe COVID-19. T-cell proliferation is telomere length (TL)-dependent and TL shortens with age. Older persons are disproportionally affected by severe COVID-19, and we hypothesized that those with short TL have less capacity to mount an adequate T-cell proliferative response to SARS-CoV-2. This hypothesis predicts that among older patients with COVID-19, shorter telomeres of peripheral blood mononuclear cells (PBMCs) will be associated with a lower lymphocyte count. METHODS: Our sample comprised 17 COVID-19 and 21 non-COVID-19 patients, aged 87(8) (mean(SD)) and 87 (9) years, respectively. We measured TL by the Telomere Shortest Length Assay, a novel method that measures and tallies the short telomeres directly relevant to telomere-mediated biological processes. The primary analysis quantified TL as the proportion of telomeres shorter than 2 kilobases. For comparison, we also quantified TL by Southern blotting, which measures the mean length of telomeres. RESULTS: Lymphocyte count (109/L) was 0.91 (0.42) in COVID-19 patients and 1.50(0.50) in non-COVID-19 patients (P < 0.001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kilobases (P = 0.005) and positively correlated with the mean of telomeres measured by TeSLA (P = 0.03). Lymphocyte counts showed no statistically significant correlations with Southern blotting results in COVID-19 or non-COVID-19 patients. CONCLUSIONS: These results support the hypothesis that a compromised TL-dependent T-cell proliferative response contributes to lymphopenia and the resulting disproportionate severity of COVID-19 among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons.

Atypical clinical presentation of COVID-19 infection in residents of a long-term care facility.

PURPOSE: To assess the magnitude of the infection in residents from-and staff working in-a long-term-care facility (LTCF) 7 days after the identification of one resident with confirmed COVID-19 infection and to assess the clinical presentation of the infected residents. METHODS: All residents and staff members of a LTCF were tested for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab. Residents were studied clinically 4 weeks after the first COVID diagnosis. RESULTS: Thirty-eight of the 79 residents (48.1%) tested positive for SARS-CoV-2. Respiratory symptoms were preceded by diarrhea (26.3%), a fall (18.4%), fluctuating temperature with hypothermia (34.2%) and delirium in one resident. Respiratory symptoms, including cough and oxygen desaturation, appeared after those initial symptoms or as the first sign in 36.8% and 52.2%, respectively. At any time of the disease, fever was observed in 65.8%. Twelve deaths occurred among the COVID-19 residents. Among the 41 residents negative for SARS-CoV-2, symptoms included cough (21.9%), diarrhea (7.3%), fever (21.9%), hypothermia (9.7%), and transient hypoxemia (9.8%). No deaths were observed in this group. 27.5% of the workers were also COVID-19 positive. CONCLUSION: The rapid dissemination of the COVID-19 infection may be explained by the delay in the diagnosis of the first cases due to atypical presentation. Early recognition of symptoms compatible with COVID-19 may help to diagnose COVID-19 residents earlier and test for SARS-CoV-2 symptomatic and asymptomatic staff and residents earlier to implement appropriate infection control practices.

Efficacy of a Test-Retest Strategy in Residents and Health Care Personnel of a Nursing Home Facing a COVID-19 Outbreak.

OBJECTIVE: To assess the American Testing Guidance for Nursing Homes (NHs)-updated May 19, 2020-with a new COVID-19 case. DESIGN: Case investigation. SETTING AND SUBJECTS: All 79 residents and 34 health care personnel (HCP) of an NH. METHODS: Seven days after identification of a COVID-19 resident, all residents and HCP underwent real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing for SARS-CoV-2 with nasopharyngeal swabs. This was repeated weekly in all previously negative subjects until the testing identified no new cases, and in all positive subjects until the testing was negative. COVID-19 infection prevention and control (IPC) measures were implemented in all residents and HCP with positive testing or with COVID-19 symptoms. Standard IPC was also implemented in all HCP. Six weeks after initial testing, all residents underwent testing for enzyme-linked immunosorbent assay-based IgG antibodies directed against the SARS-CoV-2. Symptoms were serially recorded in residents and HCP. RESULTS: A total of 36 residents had a positive rRT-PCR at baseline and 2 at day 7. Six HCP had a positive rRT-PCR at baseline and 2 at day 7. No new COVID-19 cases were diagnosed later. Among the SARS-CoV-2-positive cases, 6 residents (16%) and 3 HCP (37%) were asymptomatic during the 14 days before testing. Twenty-five residents (92.3%) and all 8 HCP (100%) with a positive rRT-PCR developed IgG antibodies against SARS-CoV-2. Among the residents and HCP always having tested negative, 2 (5%) and 5 (11.5%), respectively, developed IgG antibodies against SARS-CoV-2. These 2 residents had typical COVID-19 symptoms before and after testing and 2/5 HCP were asymptomatic before and after testing. CONCLUSIONS AND IMPLICATIONS: This study shows the validity of the updated American Testing Guidance for Nursing Homes (NHs). It suggests implementing COVID-19 IPC in both residents and HCP with positive testing or COVID-19 symptoms and warns that asymptomatic HCP with repeated negative rRT-PCR testing can develop antibodies against SARS-CoV-2.