COVID-19 research news in brief: 3rd edition

From the New England Journal of Medicine

Compassionate use of remdesivir for patients with severe COVID-19: “Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the US, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. In this cohort of patients hospitalized for severe COVID-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%).” OPEN ACCESS here.

Universal masking in hospitals in the COVID-19 era: “Masks are not only tools, they are also talismans that may help increase health care workers’ perceived sense of safety, well-being, and trust in their hospitals. Although such reactions may not be strictly logical, we are all subject to fear and anxiety, especially during times of crisis. One might argue that fear and anxiety are better countered with data and education than with a marginally beneficial mask, particularly in light of the worldwide mask shortage, but it is difficult to get clinicians to hear this message in the heat of the current crisis. Expanded masking protocols’ greatest contribution may be to reduce the transmission of anxiety, over and above whatever role they may play in reducing transmission of COVID-19. The potential value of universal masking in giving health care workers the confidence to absorb and implement the more foundational infection-prevention practices described above may be its greatest contribution.” OPEN ACCESS here.

COVID-19 and immunity in aging populations — a new research agenda: “In the long term … we will have to shift from investing primarily in disease-specific research to simultaneously targeting sufficient resources toward decoding the human immune system, particularly for the world’s most vulnerable populations. Such an effort could accelerate the development of new vaccines, diagnostics, and treatments — not just for Covid-19, but also for future emerging pathogens as well as the noncommunicable diseases of aging that are our major global killers. We need bold action as soon as possible to help all of humanity live longer and healthier lives.” OPEN ACCESS here.

The untold toll — the pandemic’s effects on patients without COVID-19: “Perhaps the greatest challenge, then, is an invisible one: How do we help people who are afraid to seek care to begin with? To date, much public health messaging regarding COVID has focused on social distancing, hand hygiene, PPE for health care workers, and the need for increased testing. Yet as we begin to observe fewer admissions for common emergencies such as heart attack and stroke, the need for vigilance about viral transmission need not detract from an equally important message: COVID or no COVID, we are still here to care for you.” OPEN ACCESS here.

Clinical characteristics of COVID-19 in New York City: “Among these 393 patients with COVID-19 who were hospitalised in two New York City hospitals, the manifestations of the disease at presentation were generally similar to those in a large case series from China; however, gastrointestinal symptoms appeared to be more common than in China (where these symptoms occurred in 4 to 5% of patients). This difference could reflect geographic variation or differential reporting. Obesity was common and may be a risk factor for respiratory failure leading to invasive mechanical ventilation. The percentage of patients in our case series who received invasive mechanical ventilation was more than 10 times as high as that in China; potential contributors include the more severe disease in our cohort (since testing and hospitalisation in the [US] is largely limited to patients with more severe disease) and the early-intubation strategy used in our hospitals. Regardless, the high demand for invasive mechanical ventilation has the potential to overwhelm hospital resources. Deterioration occurred in many patients whose condition had previously been stable; almost a third of patients who received invasive mechanical ventilation did not need supplemental oxygen at presentation. The observations that the patients who received invasive mechanical ventilation almost universally received vasopressor support and that many also received new renal replacement therapy suggest that there is also a need to strengthen stockpiles and supply chains for these resources.” OPEN ACCESS here.

From JAMA

Symptom screening at illness onset of health care personnel with SARS-CoV-2 infection in King County, Washington: “In this cohort, screening only for fever, cough, shortness of breath, or sore throat might have missed 17% of symptomatic [health care personnel (HCP)] at the time of illness onset; expanding criteria for symptoms screening to include myalgias and chills may still have missed 10%. The data indicate that HCP worked for several days while symptomatic, when, according to a growing body of evidence, they may transmit SARS-CoV-2 to vulnerable patients and other HCP. Interventions to prevent transmission from HCP include expanding symptoms-based screening criteria, furloughing symptomatic HCP, facilitating testing of symptomatic HCP, and creating sick leave policies that are nonpunitive, flexible, and consistent with public health guidance. Face mask use by all HCP for source control might prevent transmission from mildly symptomatic and asymptomatic HCP. This may be particularly important in long-term care facility settings and regions with widespread community transmission.” OPEN ACCESS here.

Pharmacologic treatments for coronavirus disease 2019 (COVID-19): “No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomised trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.” OPEN ACCESS here.

Seasonal influenza activity during the SARS-CoV-2 outbreak in Japan: “Seasonal influenza activity was lower in 2020 than in previous years in Japan. Influenza activity may have been affected by temperature or virulence (although influenza activity in the 2019/2020 season was moderately severe in other parts of the world), but also by measures taken to constrain the [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] outbreak. While closure of schools and suspension of large events occurred late in the influenza season, awareness regarding measures to reduce the risk of disease transmission was high among the Japanese public from early in the year. Limitations of this study include lack of availability of age-specific weekly data on influenza activity and information regarding means of diagnosis. Concerns regarding the SARS-CoV-2 outbreak may have changed detection of influenza through changes in symptomatic individuals seeking medical attention or in physicians’ inclination to test for influenza.” OPEN ACCESS here.

Rates of co-infection between SARS-CoV-2 and other respiratory pathogens: “These results suggest higher rates of co-infection between SARS-CoV-2 and other respiratory pathogens than previously reported, with no significant difference in rates of SARS-CoV-2 infection in patients with and without other pathogens. The presence of a non–SARS-CoV-2 pathogen may not provide reassurance that a patient does not also have SARS-CoV-2. The study is limited to a single region. Given limited sample size, restriction to multiply tested specimens, and spatiotemporal variation in viral epidemiology, the analysis is limited in the detection of specific co-infection patterns potentially predictive of SARS-CoV-2. Nonetheless, these results suggest that routine testing for non–SARS-CoV-2 respiratory pathogens during the COVID-19 pandemic is unlikely to provide clinical benefit unless a positive result would change disease management (eg, neuraminidase inhibitors for influenza in appropriate patients).” OPEN ACCESS here.

Predictive mathematical models of the COVID-19 pandemic – underlying principles and value of projections: “Modeling studies have contributed vital insights into the COVID-19 pandemic, and will undoubtedly continue to do so. Early models pointed to areas in which infection was likely widespread before large numbers of cases were detected; contributed to estimating the reproductive number, case fatality rate, and how long the virus had been circulating in a community; and helped to establish evidence that a significant amount of transmission occurs prior to symptom onset. Mathematical models can be profoundly helpful tools to make public health decisions and ensure optimal use of resources to reduce the morbidity and mortality associated with the COVID-19 pandemic, but only if they are rigorously evaluated and valid and their projections are robust and reliable.” OPEN ACCESS here.

From the BMJ

Death and dying during the pandemic: “Finally, it is important to acknowledge that we too are human. We must look for signs of compassion fatigue in our colleagues and support each other. Sharing experiences and listening to patients, their loved ones, and our colleagues will enable us to create new ways to help people know that every death is consciously witnessed; that each of those who died mattered.” OPEN ACCESS here.

Is ethnicity linked to incidence or outcomes of COVID-19? “Clear evidence to confirm or rule out an association between ethnicity and outcome in covid-19 is important not only for the UK but also for other regions such as South Asia and Africa, where the pandemic is at an earlier stage. Efforts must be coordinated to collect an international data set that includes ethnicity. If an association is confirmed, further research will be needed to determine the causes. Meanwhile, populations of all ethnicities must continue handwashing and hygiene, social distancing and self-isolation when required. The public should also be encouraged to maintain healthy lifestyles to optimise cardiometabolic and mental health. Finally, this important information must be communicated in an accessible and culturally appropriate way.” OPEN ACCESS here.

Clinical features of COVID-19: “Available evidence from observational and modelling reports indicates that up to 12% of transmission occurs before an index case develops symptoms. This has important implications for the effectiveness of any testing strategy and for contact tracing and containment measures. To curtail active transmission of SARS-CoV-2, testing should be extended far beyond people who fit a narrow case definition and other populations currently considered at risk. The current strategy will not capture the full picture, missing a substantial number of patients with atypical presentations or few symptoms. Worse, restrictive testing criteria could lead to unrecognised cases transmitting the virus in healthcare settings or the community and to delays in appropriate patient triage and management. Broad population screening for SARS-CoV-2 infections, isolation of confirmed cases through contact tracing and quarantine combined with social distancing, and large serological studies will be critical to slowing the spread of COVID-19.” OPEN ACCESS here.

From the Lancet

Endothelial cell infection and endotheliitis in COVID-19: “Our findings show the presence of viral elements within endothelial cells and an accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. These findings suggest that SARS-CoV-2 infection facilitates the induction of endotheliitis in several organs as a direct consequence of viral involvement (as noted with presence of viral bodies) and of the host inflammatory response. In addition, induction of apoptosis and pyroptosis might have an important role in endothelial cell injury in patients with COVID-19. COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. This hypothesis provides a rationale for therapies to stabilise the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins. This strategy could be particularly relevant for vulnerable patients with pre-existing endothelial dysfunction, which is associated with male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease, all of which are associated with adverse outcomes in COVID-19.” OPEN ACCESS here.

Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: “COVID-19 transmissibility measured by Rt has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% reduction in transmissibility in the community, from an estimated R_t of 1.28 before the start of the school closures to 0.72 during the closure weeks. Similarly, a 33% reduction in transmissibility was seen based on paediatric hospitalisation rates, from an R_t of 1.10 before the start of the school closures to 0.73 after school closures. Among respondents to the surveys, 74.5%, 97.5%, and 98.8% reported wearing masks when going out, and 61.3%, 90.2%, and 85.1% reported avoiding crowded places in surveys 1 (n = 1008), 2 (n = 1000), and 3 (n = 1005), respectively. Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February 2020.” OPEN ACCESS here.

SARS-CoV-2 and viral sepsis – observations and hypotheses: “Future basic science research is needed to explore whether SARS-CoV-2 directly attacks vascular endothelial cells, and to examine the effect of SARS-CoV-2 on coagulation and virus dissemination. Clinical trials and animal experiments should be done to assess the effect of ARB and ACE inhibitors on the outcome of SARS-CoV-2 infection in vivo. Efforts should be made to confirm whether SARS-CoV-2 directly infects lymphocytes, and how it influences the adaptive immune response. The kinetics of the cytokine response during SARS-CoV-2 infection also need further investigation. The efficacy of immunomodulatory therapies should be assessed in randomised clinical trials.” OPEN ACCESS here.

Two Middle East respiratory syndrome vaccines: first step for other coronavirus vaccines? “Since the outbreak of [SARS-CoV] in 2002, the emergence and expansion of endemic and epidemic coronaviruses has been accelerating on a scale not seen for any other group of viruses with pandemic potential. In the past two decades alone, five new human coronaviruses have been discovered, three of which are highly pathogenic. The coronavirus disease 2019 (COVID-19) pandemic is just the latest example of the danger posed by zoonotic diseases, foreshadowed by the regional, but unabated, emergence of Middle East respiratory syndrome coronavirus (MERS-CoV). In recognition of its intrinsic threat to public health and as a prototypical member of the family Coronaviridae, [the World Health Organization], in 2015, prioritised MERS-CoV as a pathogen to which increased resources should be dedicated for countermeasure research and development. The newly established Coalition for Epidemic Preparedness Innovations followed suit with investments in the development of candidate MERS-CoV vaccines. In subsequent years, three vaccine candidates have completed initial clinical evaluation and are now ready for advanced testing.” OPEN ACCESS here.