COVID-19 and Older Adults: What We Know.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes COVID-19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE-2 receptor, the very receptor that the SARS-CoV-2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID-19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID-19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926-929, 2020.

2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

The effect of care transition pathway implementation on patients undergoing joint replacement during the COVID-19 pandemic: a quasi-experimental study from a tertiary care hospital orthopedic department in Beijing, China.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has had a massive impact on individuals globally. The Chinese government has formulated effective response measures, and medical personnel have been actively responding to challenges associated with the epidemic prevention and control strategies. This study aimed to evaluate the effect of the implementation of a care transition pathway on patients that underwent joint replacement during the COVID-19 pandemic. METHODS: A quasi-experimental study was designed to evaluate the effect of implementing a care transition pathway for patients who underwent joint replacement during the COVID-19 pandemic in the orthopedic department of a tertiary care hospital in Beijing, China. Using a convenient sampling method, a total of 96 patients were selected. Of these, 51 patients who had undergone joint replacement in 2019 and received treatment via the routine nursing path were included in the control group. The remaining 45 patients who underwent joint replacement during the COVID-19 epidemic in 2020 and received therapy via the care transition pathway due to the implementation of epidemic prevention and control measures were included in the observation group. The quality of care transition was assessed by the Care Transition Measure (CTM), and patients were followed up 1 week after discharge. RESULTS: The observation group was determined to have better general self-care preparation, written planning materials, doctor-patient communication, health monitoring, and quality of care transition than the control group. CONCLUSIONS: A care transition pathway was developed to provide patients with care while transitioning through periods of treatment. It improved the patient perceptions of nursing quality. The COVID-19 pandemic is a huge challenge for health professionals, but we have the ability to improve features of workflows to provide the best possible patient care.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.

BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are being investigated as potential therapies for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of these interventions is required.  OBJECTIVES: Using a living systematic review approach, to assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19; and to maintain the currency of the evidence. SEARCH METHODS: To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, the Cochrane COVID-19 Study Register, the Epistemonikos COVID-19 L*OVE Platform, and trial registries. Searches were done on 17 March 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating convalescent plasma or hyperimmune immunoglobulin for COVID-19, irrespective of disease severity, age, gender or ethnicity. For safety assessments, we also included non-controlled non-randomised studies of interventions (NRSIs) if 500 or more participants were included. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of Bias 2' tool for RCTs, and for NRSIs, the assessment criteria for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence, using the GRADE approach, for the following outcomes: all-cause mortality, improvement and worsening of clinical status (for individuals with moderate to severe disease), development of severe clinical COVID-19 symptoms (for individuals with asymptomatic or mild disease), quality of life (including fatigue and functional independence), grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS: We included 13 studies (12 RCTs, 1 NRSI) with 48,509 participants, of whom 41,880 received convalescent plasma. We did not identify any completed studies evaluating hyperimmune immunoglobulin. We identified a further 100 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, and 33 studies reporting as being completed or terminated. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease Eleven RCTs and one NRSI investigated the use of convalescent plasma for 48,349 participants with moderate to severe disease. Nine RCTs compared convalescent plasma to placebo treatment or standard care alone, and two compared convalescent plasma to standard plasma (results not included in abstract). Effectiveness of convalescent plasma We included data on nine RCTs (12,875 participants) to assess the effectiveness of convalescent plasma compared to placebo or standard care alone.  Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.05; 7 RCTs, 12,646 participants; high-certainty evidence). It has little to no impact on clinical improvement for all participants when assessed by liberation from respiratory support (RR not estimable; 8 RCTs, 12,682 participants; high-certainty evidence). It has little to no impact on the chance of being weaned or liberated from invasive mechanical ventilation for the subgroup of participants requiring invasive mechanical ventilation at baseline (RR 1.04, 95% CI 0.57 to 1.93; 2 RCTs, 630 participants; low-certainty evidence). It does not reduce the need for invasive mechanical ventilation (RR 0.98, 95% CI 0.89 to 1.08; 4 RCTs, 11,765 participants; high-certainty evidence). We did not identify any subgroup differences.  We did not identify any studies reporting quality of life, and therefore, do not know whether convalescent plasma has any impact on quality of life. One RCT assessed resolution of fatigue on day 7, but we are very uncertain about the effect (RR 1.21, 95% CI 1.02 to 1.42; 309 participants; very low-certainty evidence).  Safety of convalescent plasma We included results from eight RCTs, and one NRSI, to assess the safety of convalescent plasma. Some of the RCTs reported on safety data only for the convalescent plasma group.  We are uncertain whether convalescent plasma increases or reduces the risk of grade 3 and 4 adverse events (RR 0.90, 95% CI 0.58 to 1.41; 4 RCTs, 905 participants; low-certainty evidence), and serious adverse events (RR 1.24, 95% CI 0.81 to 1.90; 2 RCTs, 414 participants; low-certainty evidence).  A summary of reported events of the NRSI (reporting safety data for 20,000 of 35,322 transfused participants), and four RCTs reporting safety data only for transfused participants (6125 participants) are included in the full text. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and asymptomatic or mild disease We identified one RCT reporting on 160 participants, comparing convalescent plasma to placebo treatment (saline).  Effectiveness of convalescent plasma We are very uncertain about the effect of convalescent plasma on all-cause mortality (RR 0.50, 95% CI 0.09 to 2.65; very low-certainty evidence). We are uncertain about the effect of convalescent plasma on developing severe clinical COVID-19 symptoms (RR not estimable; low-certainty evidence).  We identified no study reporting quality of life.  Safety of convalescent plasma We do not know whether convalescent plasma is associated with a higher risk of grade 3 or 4 adverse events (very low-certainty evidence), or serious adverse events (very low-certainty evidence). This is a living systematic review. We search weekly for new evidence and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. AUTHORS' CONCLUSIONS: We have high certainty in the evidence that convalescent plasma for the treatment of individuals with moderate to severe disease does not reduce mortality and has little to no impact on measures of clinical improvement. We are uncertain about the adverse effects of convalescent plasma. While major efforts to conduct research on COVID-19 are being made, heterogeneous reporting of outcomes is still problematic. There are 100 ongoing studies and 33 studies reporting in a study registry as being completed or terminated. Publication of ongoing studies might resolve some of the uncertainties around hyperimmune immunoglobulin therapy for people with any disease severity, and convalescent plasma therapy for people with asymptomatic or mild disease.

Psychosocial Effects of the COVID-19 Pandemic: Large-scale Quasi-Experimental Study on Social Media.

BACKGROUND: The COVID-19 pandemic has caused several disruptions in personal and collective lives worldwide. The uncertainties surrounding the pandemic have also led to multifaceted mental health concerns, which can be exacerbated with precautionary measures such as social distancing and self-quarantining, as well as societal impacts such as economic downturn and job loss. Despite noting this as a "mental health tsunami", the psychological effects of the COVID-19 crisis remain unexplored at scale. Consequently, public health stakeholders are currently limited in identifying ways to provide timely and tailored support during these circumstances. OBJECTIVE: Our study aims to provide insights regarding people's psychosocial concerns during the COVID-19 pandemic by leveraging social media data. We aim to study the temporal and linguistic changes in symptomatic mental health and support expressions in the pandemic context. METHODS: We obtained about 60 million Twitter streaming posts originating from the United States from March 24 to May 24, 2020, and compared these with about 40 million posts from a comparable period in 2019 to attribute the effect of COVID-19 on people's social media self-disclosure. Using these data sets, we studied people's self-disclosure on social media in terms of symptomatic mental health concerns and expressions of support. We employed transfer learning classifiers that identified the social media language indicative of mental health outcomes (anxiety, depression, stress, and suicidal ideation) and support (emotional and informational support). We then examined the changes in psychosocial expressions over time and language, comparing the 2020 and 2019 data sets. RESULTS: We found that all of the examined psychosocial expressions have significantly increased during the COVID-19 crisis-mental health symptomatic expressions have increased by about 14%, and support expressions have increased by about 5%, both thematically related to COVID-19. We also observed a steady decline and eventual plateauing in these expressions during the COVID-19 pandemic, which may have been due to habituation or due to supportive policy measures enacted during this period. Our language analyses highlighted that people express concerns that are specific to and contextually related to the COVID-19 crisis. CONCLUSIONS: We studied the psychosocial effects of the COVID-19 crisis by using social media data from 2020, finding that people's mental health symptomatic and support expressions significantly increased during the COVID-19 period as compared to similar data from 2019. However, this effect gradually lessened over time, suggesting that people adapted to the circumstances and their "new normal." Our linguistic analyses revealed that people expressed mental health concerns regarding personal and professional challenges, health care and precautionary measures, and pandemic-related awareness. This study shows the potential to provide insights to mental health care and stakeholders and policy makers in planning and implementing measures to mitigate mental health risks amid the health crisis.

Taking Language Samples Home: Feasibility, Reliability, and Validity of Child Language Samples Conducted Remotely With Video Chat Versus In-Person.

Purpose There has been increased interest in using telepractice for involving more diverse children in research and clinical services, as well as when in-person assessment is challenging, such as during COVID-19. Little is known, however, about the feasibility, reliability, and validity of language samples when conducted via telepractice. Method Child language samples from parent-child play were recorded either in person in the laboratory or via video chat at home, using parents' preferred commercially available software on their own device. Samples were transcribed and analyzed using Systematic Analysis of Language Transcripts software. Analyses compared measures between-subjects for 46 dyads who completed video chat language samples versus 16 who completed in-person samples; within-subjects analyses were conducted for a subset of 13 dyads who completed both types. Groups did not differ significantly on child age, sex, or socioeconomic status. Results The number of usable samples and percent of utterances with intelligible audio signal did not differ significantly for in-person versus video chat language samples. Child speech and language characteristics (including mean length of utterance, type-token ratio, number of different words, grammatical errors/omissions, and child speech intelligibility) did not differ significantly between in-person and video chat methods. This was the case for between-group analyses and within-child comparisons. Furthermore, transcription reliability (conducted on a subset of samples) was high and did not differ between in-person and video chat methods. Conclusions This study demonstrates that child language samples collected via video chat are largely comparable to in-person samples in terms of key speech and language measures. Best practices for maximizing data quality for using video chat language samples are provided.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

Vitamin D and survival in COVID-19 patients: A quasi-experimental study.

Vitamin D may be a central biological determinant of COVID-19 outcomes. The objective of this quasi-experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before COVID-19 was effective in improving survival among frail elderly nursing-home residents with COVID-19. Sixty-six residents with COVID-19 from a French nursing-home were included in this quasi-experimental study. The "Intervention group" was defined as those having received bolus vitamin D3 supplementation during COVID-19 or in the preceding month, and the "Comparator group" corresponded to all other participants. The primary and secondary outcomes were COVID-19 mortality and Ordinal Scale for Clinical Improvement (OSCI) score in acute phase, respectively. Age, gender, number of drugs daily taken, functional abilities, albuminemia, use of corticosteroids and/or hydroxychloroquine and/or antibiotics (i.e., azithromycin or rovamycin), and hospitalization for COVID-19 were used as potential confounders. The Intervention (n = 57; mean ± SD, 87.7 ± 9.3years; 79 %women) and Comparator (n = 9; mean, 87.4 ± 7.2years; 67 %women) groups were comparable at baseline, as were the COVID-19 severity and the use of dedicated COVID-19 drugs. The mean follow-up time was 36 ± 17 days. 82.5 % of participants in the Intervention group survived COVID-19, compared to only 44.4 % in the Comparator group (P = 0.023). The full-adjusted hazard ratio for mortality according to vitamin D3 supplementation was HR = 0.11 [95 %CI:0.03;0.48], P = 0.003. Kaplan-Meier distributions showed that Intervention group had longer survival time than Comparator group (log-rank P = 0.002). Finally, vitamin D3 supplementation was inversely associated with OSCI score for COVID-19 (ß=-3.84 [95 %CI:-6.07;-1.62], P = 0.001). In conclusion, bolus vitamin D3 supplementation during or just before COVID-19 was associated in frail elderly with less severe COVID-19 and better survival rate.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.

BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.  OBJECTIVES: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. SEARCH METHODS: We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 19 August 2020. SELECTION CRITERIA: We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' 2.0 tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, mortality (time to event), improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events (AEs), and serious adverse events (SAEs). MAIN RESULTS: This is the second living update of our review. We included 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma. Two completed RCTs are awaiting assessment (published after 19 August 2020). We identified a further 138 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 73 are randomised (3 reported in a study registry as already being completed, but without results). We did not identify any completed studies evaluating hyperimmune immunoglobulin. We did not include data from controlled NRSIs in data synthesis because of critical risk of bias. The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms.  Effectiveness of convalescent plasma for people with COVID-19  We included results from two RCTs (both stopped early) with 189 participants, of whom 95 received convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. We are uncertain whether convalescent plasma decreases all-cause mortality at hospital discharge (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.22 to 1.34; 1 RCT, 86 participants; low-certainty evidence).  We are uncertain whether convalescent plasma decreases mortality (time to event) (hazard ratio (HR) 0.64, 95% CI 0.33 to 1.25; 2 RCTs, 189 participants; low-certainty evidence). Convalescent plasma may result in little to no difference in improvement of clinical symptoms (i.e. need for respiratory support) at seven days (RR 0.98, 95% CI 0.30 to 3.19; 1 RCT, 103 participants; low-certainty evidence). Convalescent plasma may increase improvement of clinical symptoms at up to 15 days (RR 1.34, 95% CI 0.85 to 2.11; 2 RCTs, 189 participants; low-certainty evidence), and at up to 30 days (RR 1.13, 95% CI 0.88 to 1.43; 2 studies, 188 participants; low-certainty evidence).  No studies reported on quality of life.  Safety of convalescent plasma for people with COVID-19 We included results from two RCTs, eight controlled NRSIs and nine non-controlled NRSIs assessing safety of convalescent plasma. Reporting of safety data and duration of follow-up was variable. The controlled studies reported on AEs and SAEs only in participants receiving convalescent plasma. Some, but not all, studies included death as a SAE.  The studies did not report the grade of AEs. Fourteen studies (566 participants) reported on AEs of possible grade 3 or 4 severity. The majority of these AEs were allergic or respiratory events. We are very uncertain whether convalescent plasma therapy affects the risk of moderate to severe AEs (very low-certainty evidence).  17 studies (35,944 participants) assessed SAEs for 20,622 of its participants. The majority of participants were from one non-controlled NRSI (20,000 participants), which reported on SAEs within the first four hours and within an additional seven days after transfusion. There were 63 deaths, 12 were possibly and one was probably related to transfusion. There were 146 SAEs within four hours and 1136 SAEs within seven days post-transfusion. These were predominantly allergic or respiratory, thrombotic or thromboembolic and cardiac events. We are uncertain whether convalescent plasma therapy results in a clinically relevant increased risk of SAEs (low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. There was limited information regarding grade 3 and 4 AEs to determine the effect of convalescent plasma therapy on clinically relevant SAEs. In the absence of a control group, we are unable to assess the relative safety of convalescent plasma therapy.  While major efforts to conduct research on COVID-19 are being made, recruiting the anticipated number of participants into these studies is problematic. The early termination of the first two RCTs investigating convalescent plasma, and the lack of data from 20 studies that have completed or were due to complete at the time of this update illustrate these challenges. Well-designed studies should be prioritised. Moreover, studies should report outcomes in the same way, and should consider the importance of maintaining comparability in terms of co-interventions administered in all study arms.  There are 138 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 73 are RCTs (three already completed). This is the second living update of the review, and we will continue to update this review periodically. Future updates may show different results to those reported here.

Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study.

BACKGROUND: The management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals, these delays lead to poor patient flow and nosocomial transmission. Rapid, accurate tests are therefore urgently needed in preparation for the next wave of the pandemic. METHODS: We did a prospective, interventional, non-randomised, controlled study of molecular point-of-care testing in patients aged 18 years or older presenting with suspected COVID-19 to the emergency department or other acute areas of Southampton General Hospital during the first wave of the pandemic in the UK. Nose and throat swab samples taken at admission from patients in the point-of-care testing group were tested with the QIAstat-Dx Respiratory SARS-CoV-2 Panel. Samples taken from patients in a contemporaneous control group were tested by laboratory PCR. The primary outcome was time to results in the full cohort. This study is registered with ISRCTN (ISRCTN14966673) and is completed. FINDINGS: Between March 20 and April 29, 2020, 517 patients were assessed for eligibility, of whom 499 were recruited to the point-of-care testing group and tested by the QIAstat-Dx Respiratory SARS-CoV-2 Panel. 555 contemporaneously identified patients were included in the control group and tested by laboratory PCR. The two groups were similar with regard to the distribution of sex, age, and ethnicity. 197 (39%) patients in the point-of-care testing group and 155 (28%) in the control group tested positive for COVID-19 (difference 11·5% [95% CI 5·8-17·2], p=0·0001). Median time to results was 1·7 h (IQR 1·6-1·9) in the point-of-care testing group and 21·3 h (16·0-27·9) in the control group (difference 19·6 h [19·0-20·3], p<0·0001). A Cox proportional hazards regression model controlling for age, sex, time of presentation, and severity of illness also showed that time to results was significantly shorter in the point-of-care testing group than in the control group (hazard ratio 4023 [95% CI 545-29 696], p<0·0001). INTERPRETATION: Point-of-care testing is associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralised laboratory PCR testing. FUNDING: University Hospitals Southampton NHS Foundation Trust.

Comparing Associations of State Reopening Strategies with COVID-19 Burden.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) infected over 5 million United States (US) residents resulting in more than 180,000 deaths by August 2020. To mitigate transmission, most states ordered shelter-in-place orders in March and reopening strategies varied. OBJECTIVE: To estimate excess COVID-19 cases and deaths after reopening compared with trends prior to reopening for two groups of states: (1) states with an evidence-based reopening strategy, defined as reopening indoor dining after implementing a statewide mask mandate, and (2) states reopening indoor dining rooms before implementing a statewide mask mandate. DESIGN: Interrupted time series quasi-experimental study design applied to publicly available secondary data. PARTICIPANTS: Fifty United States and the District of Columbia. INTERVENTIONS: Reopening indoor dining rooms before or after implementing a statewide mask mandate. MAIN MEASURES: Outcomes included daily cumulative COVID-19 cases and deaths for each state. KEY RESULTS: On average, the number of excess cases per 100,000 residents in states reopening without masks is ten times the number in states reopening with masks after 8 weeks (643.1 cases; 95% confidence interval (CI) = 406.9, 879.2 and 62.9 cases; CI = 12.6, 113.1, respectively). Excess cases after 6 weeks could have been reduced by 90% from 576,371 to 63,062 and excess deaths reduced by 80% from 22,851 to 4858 had states implemented mask mandates prior to reopening. Over 50,000 excess deaths were prevented within 6 weeks in 13 states that implemented mask mandates prior to reopening. CONCLUSIONS: Additional mitigation measures such as mask use counteract the potential growth in COVID-19 cases and deaths due to reopening businesses. This study contributes to the growing evidence that mask usage is essential for mitigating community transmission of COVID-19. States should delay further reopening until mask mandates are fully implemented, and enforcement by local businesses will be critical for preventing potential future closures.

Effectiveness of the non-pharmaceutical public health interventions against COVID-19; a protocol of a systematic review and realist review.

BACKGROUND: Without any pharmaceutical intervention and vaccination, the only way to combat Coronavirus Disease 2019 (COVID-19) is to slow down the spread of the disease by adopting non-pharmaceutical public health interventions (PHIs). Patient isolation, lockdown, quarantine, social distancing, changes in health care provision, and mass screening are the most common non-pharmaceutical PHIs to cope with the epidemic. However, there is neither systematic evidence on the effectiveness of non-pharmaceutical PHIs in controlling the COVID-19 nor on how these interventions work in different contexts. Therefore, in this study we will address two main objectives: 1) to assess the effectiveness of the non-pharmaceutical PHIs in controlling the spread of COVID-19 using a systematic review and meta-analyses; 2) to explore why, how, and for whom these interventions work using a realist review. MATERIALS AND METHODS: This review study has two main phases. In the first phase of this study, we will extract data from two main types of studies including quasi-experimental studies (such as quasi-randomized trials, controlled before-after studies (CBAs) and interrupted time series studies (ITSs)) and observational studies (such as cohort, case-control, and cross-sectional studies), written in the English language. We will explore effectiveness of the non-pharmaceutical PHIs targeted either suppression or mitigation strategies (or a combination of both) in controlling the COVID-19 epidemics in the community level. Effectiveness will be considered as the changes in mortality rate, incidence rate, basic reproduction number rate, morbidity rate, rates of hospitalization, rates of intensive care unit (ICU) hospitalization, and other health outcomes where possible. We will perform random-effects meta-analyses, if possible, using CMA software. In the second phase, we will conduct a realist review to find out how, why, for whom, and in what circumstances the non-pharmaceutical PHIs work. At the realist review, we will identify and explore Context-Mechanism-Outcome configurations to provide a robust explanation on the effectiveness of the interventions in different contexts using Pawson's 5-step realist review template including: "clarify scope; search for evidence; appraise primary studies and extract data; synthesize evidence and draw conclusions; and disseminate, implement and evaluate". Although the steps are presented in a linear manner, in practice, we will follow them in iterative stages to fill any potential overlap. DISCUSSION: The findings of this research will provide a crucial insight into how and in which context the non-pharmaceutical PHIs work in controlling the spread of COVID-19. Conducting a systematic review and meta-analysis in line with a realist review will allow us to draw a robust conclusion on the effects and the way in which the interventions work. Understanding the role of contextual factors in the effectiveness of non-pharmaceutical PHIs and the mechanism of this process could enable policymakers to implement appropriate policies and manage the COVID-19 epidemics more efficiently. SYSTEMATIC REVIEW REGISTRATION: CRD42020186855.

Pride and Prejudice during the COVID-19 Pandemic: The Misfortune of Inappropriate Clinical Trial Design.

Coronavirus Disease 2019 (COVID-19) is a rapidly evolving global pandemic for which more than a thousand clinical trials have been registered to secure therapeutic effectiveness, expeditiously. Most of these are single-center non-randomized studies rather than multi-center, randomized controlled trials. Single-arm trials have several limitations and may be conducted when spontaneous improvement is not anticipated, small placebo effect exists, and randomization to a placebo is not ethical. In an emergency where saving lives takes precedence, it is ethical to conduct trials with any scientifically proven design, however, safety must not be compromised. A phase II or III trial can be conducted directly in a pandemic with appropriate checkpoints and stopping rules. COVID-19 has two management paradigms- antivirals, or treatment of its complications. Simultaneous assessment of two different treatments can be done using 2 × 2 factorial schema. World Health Organization's SOLIDARITY trial is a classic example of the global research protocol which can evaluate the preferred treatment to combat COVID-19 pandemic. Short of that, a trial design must incorporate the practicality of the intervention used, and an appropriate primary endpoint which should ideally be a clinical outcome. Collaboration between institutions is needed more than ever to successfully execute and accrue in randomized trials.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.

BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.  OBJECTIVES: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. SEARCH METHODS: We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 4 June 2020. SELECTION CRITERIA: We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs.  MAIN RESULTS: This is the first living update of our review. We included 20 studies (1 RCT, 3 controlled NRSIs, 16 non-controlled NRSIs) with 5443 participants, of whom 5211 received convalescent plasma, and identified a further 98 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 50 are randomised. We did not identify any completed studies evaluating hyperimmune immunoglobulin. Overall risk of bias of included studies was high, due to study design, type of participants, and other previous or concurrent treatments. Effectiveness of convalescent plasma for people with COVID-19  We included results from four controlled studies (1 RCT (stopped early) with 103 participants, of whom 52 received convalescent plasma; and 3 controlled NRSIs with 236 participants, of whom 55 received convalescent plasma) to assess effectiveness of convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. All-cause mortality at hospital discharge (1 controlled NRSI, 21 participants) We are very uncertain whether convalescent plasma has any effect on all-cause mortality at hospital discharge (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.61 to 1.31; very low-certainty evidence). Time to death (1 RCT, 103 participants; 1 controlled NRSI, 195 participants) We are very uncertain whether convalescent plasma prolongs time to death (RCT: hazard ratio (HR) 0.74, 95% CI 0.30 to 1.82; controlled NRSI: HR 0.46, 95% CI 0.22 to 0.96; very low-certainty evidence). Improvement of clinical symptoms, assessed by need for respiratory support (1 RCT, 103 participants; 1 controlled NRSI, 195 participants) We are very uncertain whether convalescent plasma has any effect on improvement of clinical symptoms at seven days (RCT: RR 0.98, 95% CI 0.30 to 3.19), 14 days (RCT: RR 1.85, 95% CI 0.91 to 3.77; controlled NRSI: RR 1.08, 95% CI 0.91 to 1.29), and 28 days (RCT: RR 1.20, 95% CI 0.80 to 1.81; very low-certainty evidence). Quality of life No studies reported this outcome.  Safety of convalescent plasma for people with COVID-19 We included results from 1 RCT, 3 controlled NRSIs and 10 non-controlled NRSIs assessing safety of convalescent plasma. Reporting of adverse events and serious adverse events was variable. The controlled studies reported on adverse events and serious adverse events only in participants receiving convalescent plasma. The duration of follow-up varied. Some, but not all, studies included death as a serious adverse event.  Grade 3 or 4 adverse events (13 studies, 201 participants) The studies did not report the grade of adverse events. Thirteen studies (201 participants) reported on adverse events of possible grade 3 or 4 severity. The majority of these adverse events were allergic or respiratory events. We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence).  Serious adverse events (14 studies, 5201 participants)  Fourteen studies (5201 participants) reported on serious adverse events. The majority of participants were from one non-controlled NRSI (5000 participants), which reported only on serious adverse events limited to the first four hours after convalescent plasma transfusion. This study included death as a serious adverse event; they reported 15 deaths, four of which they classified as potentially, probably or definitely related to transfusion. Other serious adverse events reported in all studies were predominantly allergic or respiratory in nature, including anaphylaxis, transfusion-associated dyspnoea, and transfusion-related acute lung injury (TRALI). We are very uncertain whether or not convalescent plasma affects the number of serious adverse events. AUTHORS' CONCLUSIONS: We are very uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. For safety outcomes we also included non-controlled NRSIs. There was limited information regarding adverse events. Of the controlled studies, none reported on this outcome in the control group. There is only very low-certainty evidence for safety of convalescent plasma for COVID-19.  While major efforts to conduct research on COVID-19 are being made, problems with recruiting the anticipated number of participants into these studies are conceivable. The early termination of the first RCT investigating convalescent plasma, and the multitude of studies registered in the past months illustrate this. It is therefore necessary to critically assess the design of these registered studies, and well-designed studies should be prioritised. Other considerations for these studies are the need to report outcomes for all study arms in the same way, and the importance of maintaining comparability in terms of co-interventions administered in all study arms.  There are 98 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 50 are RCTs. This is the first living update of the review, and we will continue to update this review periodically. These updates may show different results to those reported here.

What do we know about COVID-19? A review article.

OBJECTIVES: To bring summarized information about what has been published so far regarding Covid-19, facilitating the access to information and a better understanding of this pandemic, and to contribute to the medical community in the decision-making against this virus. METHODS: This review article brings collected information from different articles published since the beginning of the pandemic of the 2019 novel coronavirus. KEY RESULTS: This paper aggregates and consolidates some epidemiological parameters and clinical knowledge about the novel coronavirus and brings what is new in the search for pandemic control. MAJOR CONCLUSIONS: Governments and health authorities are under increased pressure to control the COVID-19 spreading. In this scenario, the scientific community is working hard to produce relevant papers which will help in the next steps against coronavirus. Our review summarized the latest news about SARS-CoV2, evidencing what we know about COVID-19 until now.