Research news in brief – COVID-19 2nd edition

From the New England Journal of Medicine

COVID-19 in critically ill patients in the Seattle region — case series: We identified 24 patients with confirmed COVID-19. The mean (±SD) age of the patients was 64 ± 18 years, 63% were men, and symptoms began 7 ± 4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. During the first 3 weeks of the COVID-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. OPEN ACCESS at https://www.nejm.org/doi/full/10.1056/NEJMoa2004500?query=featured_coronavirus

Age, complexity, and crisis — a prescription for progress in pandemic: During a pandemic in which 80% of US deaths are in people over 65, especially affecting those who are around 80 with underlying conditions, health leaders and clinicians might reasonably conclude that they’re too busy saving lives to also consider preventing the hazards of hospitalization for elders or their postdischarge lives. In a crisis, they might argue, different rules apply. This unprecedented crisis is exactly why we need to think now about how best to manage the care of sick elders — for their sake and in consideration of near- and longer-term costs and stresses to the health care system. Sally’s recent hospitalization didn’t just ruin her life; it’s the reason she now needs long-term respiratory and other services that might otherwise be available to patients with COVID-19. OPEN ACCESS at https://www.nejm.org/doi/full/10.1056/NEJMp2006115?query=featured_coronavirus

Renin–angiotensin–aldosterone system inhibitors in patients with COVID-19: Here, we highlight that the data in humans are too limited to support or refute these hypotheses and concerns. Specifically, we discuss the uncertain effects of [renin–angiotensin–aldosterone system (RAAS)] blockers on [angiotensin-converting enzyme 2 (ACE2)] levels and activity in humans, and we propose an alternative hypothesis that ACE2 may be beneficial rather than harmful in patients with lung injury. We also explicitly raise the concern that withdrawal of RAAS inhibitors may be harmful in certain high-risk patients with known or suspected COVID-19. OPEN ACCESS at https://www.nejm.org/doi/full/10.1056/NEJMsr2005760?query=featured_coronavirus

Epidemiology of COVID-19 in a long-term care facility in King County, Washington: As of March 18, a total of 167 confirmed cases of COVID-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with COVID-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of COVID-19 had been identified in King County. In the context of rapidly escalating COVID-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of COVID-19. OPEN ACCESS at https://www.nejm.org/doi/full/10.1056/NEJMoa2005412?query=featured_coronavirus

A trial of lopinavir–ritonavir in adults hospitalized with severe COVID-19: A total of 199 patients with laboratory-confirmed [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. In hospitalized adult patients with severe COVID-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. OPEN ACCESS at https://www.nejm.org/doi/full/10.1056/NEJMoa2001282?query=featured_coronavirus

From the BMJ

Prediction models for diagnosis and prognosis of COVID-19 infection: systematic review and critical appraisal: Prediction models for COVID-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that proposed models are poorly reported, at high risk of bias, and their reported performance is probably optimistic. Immediate sharing of well documented individual participant data from COVID-19 studies is needed for collaborative efforts to develop more rigorous prediction models and validate existing ones. The predictors identified in included studies could be considered as candidate predictors for new models. Methodological guidance should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, studies should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline. OPEN ACCESS at https://www.bmj.com/content/369/bmj.m1328

COVID-19: Why Germany’s case fatality rate seems so low: There are worrying signs of acceleration. The Robert Koch Institute’s daily COVID-19 report on 26 March showed a total of 149 deaths, meaning a fatality rate of 0.5%. In the following days the death rate edged higher, doubling from 66 deaths on 30 March to 128 the next day. The 1 April report showed 149 new deaths (a total of 732 and a 1.1% fatality rate). OPEN ACCESS at https://www.bmj.com/content/369/bmj.m1395

COVID-19: a remote assessment in primary care: This article will present some guiding principles on how to choose between telephone and video appointments, how to conduct a “query COVID” consultation remotely, and considerations when arranging follow-up and next steps. It does not cover remote triage or how to set up video consulting in your practice. This article is intended as a broad orientation to a COVID-19 consultation. It does not cover every clinical eventuality, and should not be used as an official guideline for the management of a COVID-19 patient. National and local guidance are being urgently produced, and further research is being undertaken on specific aspects of management such as use of antibiotics. OPEN ACCESS at https://www.bmj.com/content/368/bmj.m1182

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study: [SARS-CoV-2] infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of COVID-19. OPEN ACCESS at https://www.bmj.com/content/368/bmj.m1091

Managing mental health challenges faced by healthcare workers during COVID-19 pandemic: The COVID-19 pandemic is likely to put healthcare professionals across the world in an unprecedented situation, having to make impossible decisions and work under extreme pressures. These decisions may include how to allocate scant resources to equally needy patients, how to balance their own physical and mental healthcare needs with those of patients, how to align their desire and duty to patients with those to family and friends, and how to provide care for all severely unwell patients with constrained or inadequate resources. This may cause some to experience moral injury or mental health problems. OPEN ACCESS at https://www.bmj.com/content/368/bmj.m1211

From JAMA

Understanding and addressing sources of anxiety among health care professionals during the COVID-19 pandemic: This Viewpoint summarizes key considerations for supporting the health care workforce so health care professionals are equipped to provide care for their patients and communities. Few of these considerations and suggestions have substantial evidence to support them; they are based on experience, direct requests from health care professionals, and common sense. OPEN ACCESS at https://jamanetwork.com/journals/jama/fullarticle/2764380

The challenge of preventing COVID-19 spread in correctional facilities: The Centers for Disease Control and Prevention (CDC) notes that people who are incarcerated or detained in a particular facility often come from a variety of locations, increasing the chance of introducing COVID-19. Plus, options to isolate people with COVID-19 are usually limited, and many facilities restrict access to soap and paper towels and ban alcohol-based hand sanitizers. In addition, incarcerated individuals are more likely than the general population to have underlying illnesses, such as cancer, diabetes, or substance use disorder, that increase their risk of developing severe COVID-19, said Daniel Lopez Acuña, MD, MPH, who helped craft new COVID-19 guidelines for prisons and jails for the World Health Organization. OPEN ACCESS at https://jamanetwork.com/journals/jama/fullarticle/2764379

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy: What are the baseline characteristics and outcomes of patients with laboratory-confirmed [SARS-CoV-2] infection admitted to intensive care units (ICUs) in Lombardy, Italy? In this retrospective case series that involved 1591 critically ill patients admitted from February 20 to March 18, 2020, 99% (1287 of 1300 patients) required respiratory support, including endotracheal intubation in 88% and noninvasive ventilation in 11%; ICU mortality was 26%. In this case series of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed coronavirus disease 2019 (COVID-19), a high proportion required mechanical ventilation and ICU mortality was 26% as of March 25, 2020. OPEN ACCESS at https://jamanetwork.com/journals/jama/fullarticle/2764365

Critical illness in patients with COVID-19: mounting an effective clinical and research response: Transparency in reporting the experience of patients and physicians in some parts of the world helps to telegraph what could lie ahead in other parts. Thus, pandemic-focused studies that document the presentation, clinical characteristics, and prognosis of patients with COVID-19, such as this one from northern Italy, helps inform patient care elsewhere. Efforts by this consortium to gather data by telephone augmented the real-time data collection and retrospective review of hospital records that formed the basis of this report. Observations from Lombardy also inform investigators planning much-needed interventional trials by considering rates of life support utilization, fatality, and the frequency and severity of morbidity outcomes for patients with COVID-19-related critical illness. Context matters in this regard, because illness trajectories are dependent on each setting and circumstance. OPEN ACCESS at https://jamanetwork.com/journals/jama/fullarticle/2764363

Sample pooling as a strategy to detect community transmission of SARS-CoV-2: The coronavirus disease 2019 (COVID-19) pandemic has revealed the global importance of robust diagnostic testing to differentiate [SARS-CoV-2] from other routine respiratory infections and guide appropriate clinical management. Given the limited testing capacity available in the United States early in the pandemic, individuals with a clinical syndrome consistent with COVID-19, but without travel or exposure history, were not tested. Therefore, it remains uncertain whether there may have been community circulation of SARS-CoV-2 prior to the identification of individuals with positive results through standard public health surveillance. Sample pooling, a strategy used for community monitoring of other infectious diseases such as trachoma, has not, to our knowledge, been deployed for the early comprehensive screening of SARS-CoV-2 in the United States. OPEN ACCESS at https://jamanetwork.com/journals/jama/fullarticle/2764364

From the Lancet

Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations: As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill. OPEN ACCESS at https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30161-2/fulltext

School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review: In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2–4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods. OPEN ACCESS at https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30095-X/fulltext

Developing antibody tests for SARS-CoV-2: In response to coronavirus disease 2019 (COVID-19), governments have instigated rules that constrain personal freedoms and hamstring their own economies, placing approximately 3 billion people under lockdown. Some have rolled out widespread testing for current infections, while others limited these tests to people who were hospitalised, at least during the early stages of their responses. As new controls begin to bite, the race to develop and approve a test with a different purpose — to assess not current viral infection, but immunity to [SARS-CoV-2] — has heated up. Medical diagnostic companies are scrambling, and governments are looking to order these antibody tests by the millions. OPEN ACCESS at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30788-1/fulltext

Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged > 64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4.4 days (95% CI, 0.0–14.0) for the period of December 24 to January 27, to 2.6 days (0.0–9.0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5.2 days (1.8–12.4) and the mean serial interval at 5.1 days (1.3–11.6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1.08 (95% CI, 0.74–1.54) in Shenzhen city of Guangdong province and 1.71 (1.32–2.17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, < 1) after Jan 30. Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. OPEN ACCESS at https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30230-9/fulltext

COVID-19 in a patient with chronic lymphocytic leukaemia: Clinical and biochemical data of COVID-19 might be partly masked by coexisting chronic lymphocytic leukaemia; better diagnostic strategies (ie, superior CT differential techniques such as radiomics) could be used for diagnosis; individuals with compromised immune status might be subjected to a longer incubation period (although the underlying mechanisms are not known); and it remains uncertain whether the combination of chemotherapy, corticosteroids, α-interferon, and immunoglobulins could work synergistically in patients with chronic lymphocytic leukaemia and COVID-19. OPEN ACCESS at https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30074-0/fulltext