COVID-19 research news in brief

From JAMA

Analysis of genomic characteristics and transmission routes of patients with confirmed SARS-CoV-2 in Southern California during the early stage of the US COVID-19 pandemic: “This case series of 192 patients found that 82% of SARS-CoV-2 isolates from Los Angeles shared closest similarity to those originating in Europe vs those from Asia (15%). Using the variation signature of the viral genomes, two main clusters were identified, with the top variants sharing genomic features from European SARS-CoV-2 isolates, and several subclusters of SARS-CoV-2 outbreaks represented trackable community spread in Los Angeles. Meaning: These findings suggest that SARS-CoV-2 genomes in Los Angeles were predominantly related to the isolates originating from Europe, which are similar to viral strain distributions in New York, New York; a smaller subgroup of SARS-CoV-2 genomes shared similarities to those from originating from Asia, indicating multiple sources of viral introduction within the Los Angeles community.”

COVID-19 and psychological distress—changes in internet searches for mental health issues in New York during the pandemic: “Searches for ‘anxiety’ significantly increased following 22 March, 2020, and remained significantly higher than expected for 3 consecutive weeks, during which searches were on average 18% (95% PI, 5%–29%) greater than expected. Searches for ‘panic attack’ soared during the first week of the lockdown: search volumes increased 56% (95% PI, 37%–97%). They subsequently remained significantly higher for 5 consecutive weeks. During the entire lockdown, searches for ‘insomnia’ were on average 21% (95% PI, 1%–55%) higher than expected. ‘Suicide’ and ‘depression’ did not exhibit significantly different [relative search volumes] from what was expected. There was a spike in searches for ‘suicide’ during the week of 26 April through 2 May. This brief increase occurred following the publicized suicide of a New York physician, and search levels returned to normal the following week.”

Use and content of primary care office-based vs telemedicine care visits during the COVID-19 pandemic in the US: “In this cross-sectional analysis of the US National Disease and Therapeutic Index audit of more than 125.8 million primary care visits in the 10 calendar quarters between quarter 1 of 2018 and quarter 2 of 2020, primary care visits decreased by 21.4% during the second quarter of 2020 compared with the average quarterly visit volume of the second quarters of 2018 and 2019. Evaluations of blood pressure and cholesterol levels decreased owing to fewer total visits and less frequent assessment during telemedicine encounters. Meaning: The COVID-19 pandemic was associated with changes in the structure of primary care delivery during the second quarter of 2020, with the content of telemedicine visits differing from that of office-based encounters.”

Characteristics and outcomes of patients deferred for transcatheter aortic valve replacement because of COVID-19: “During the COVID-19 pandemic, vigilance is needed for patients with [aortic stenosis] awaiting TAVR [transcatheter aortic valve replacement], because 10% of our patients experienced a cardiac event during the first month, and 35% did so over the course of the next 3 months. We must be judicious when deciding to intervene, because there are additional risks to consider for both the patient and the heart team. In addition, it is necessary to resume required interventions as we pass the initial peak of COVID-19 hospitalizations and health care resources become available. The study was limited by being a single-center study with a limited sample size. Patients with advanced symptoms, lower left ventricular ejection fraction, obstructive coronary artery disease, and cerebrovascular accident history represent a high-risk population with [aortic stenosis], and the heart team should consider these factors for earlier access to TAVR during the COVID-19 pandemic.”

From the BMJ

In-hospital cardiac arrest in critically ill patients with COVID-19: multicentre cohort study: “Among 5019 critically ill patients with COVID-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation. Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14) v 60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest. Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14) v 67 (14) years). The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status. Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older. Conclusions: Cardiac arrest is common in critically ill patients with COVID-19 and is associated with poor survival, particularly among older patients.”

Drug treatments for COVID-19: living systematic review and network meta-analysis: “35 trials with 16 588 patients met inclusion criteria; 12 (24.3%) trials and 6853 (41.3%) patients are new from the previous iteration. Twenty-seven randomised controlled trials were included in the analysis performed on 29 July 2020. Compared with standard care, glucocorticoids probably reduce death (risk difference 31 fewer per 1000 patients, 95% credible interval 55 fewer to 5 fewer, moderate certainty), mechanical ventilation (28 fewer per 1000 patients, 45 fewer to 9 fewer, moderate certainty), and duration of hospitalisation (mean difference −1.0 day, −1.4 to −0.6 days moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, and length of hospital stay is uncertain, but it probably reduces duration of symptoms (−2.6 days −4.3 to −0.6 days, moderate certainty) and probably does not substantially increase adverse effects leading to drug discontinuation (3 more per 1000, 7 fewer to 43 more, moderate certainty). Hydroxychloroquine may not reduce risk of death (13 more per 1000, 15 fewer to 43 more, low certainty) or mechanical ventilation (19 more per 1000, 4 fewer to 45 more, moderate certainty). The certainty in effects for all other interventions was low or very low certainty. Conclusion: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with COVID-19 compared with standard care, whereas hydroxychloroquine may not reduce either. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important limitations.”

Risk stratification of patients admitted to hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score: “35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large = 0, slope = 1.0). Patients with a score of at least 15 (n = 4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n = 1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61–0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63–0.73). Conclusions: An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with COVID-19 into different management groups. The score should be further validated to determine its applicability in other populations.”

From the Lancet

Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial: “Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir–ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1.03, 95% CI 0.91–1.17; P = 0.60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to > 28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0.98, 95% CI 0.91–1.05; P = 0.53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1.09, 95% CI 0.99–1.20; P = 0.092). Interpretation: In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19.”

Prevalence, management, and outcomes of SARS-CoV-2 infections in older people and those with dementia in mental health wards in London, UK: A retrospective observational study: “Of 344 inpatients, 131 (38%) were diagnosed with COVID-19 during the study period (period prevalence 38% [95% CI 33–43]). The mean age of patients who had COVID-19 was 75.3 years (SD 8.2); 68 (52%) were women and 47 (36%) from ethnic minority groups. 16 (12%) of 131 patients were asymptomatic and 121 (92%) had one or more disease-related comorbidity. 108 (82%) patients were compulsorily detained. 74 (56%) patients had dementia, of whom 13 (18%) had young-onset dementia. On average, sites received COVID-19 testing kits 4.5 days after the first clinical COVID-19 presentation. 19 (15%) patients diagnosed with COVID-19 died during the study period, and their deaths were determined to be COVID-19 related. Interpretation: Patients in psychiatric inpatient settings who were admitted without known SARS-CoV-2 infection had a high risk of infection with SARS-CoV-2 compared with those in the community and had a higher proportion of deaths from COVID-19 than in the community. Implementation of the long-standing policy of parity of esteem for mental health and planning for future COVID-19 waves in psychiatric hospitals is urgent.”

Neuropathology of patients with COVID-19 in Germany: a post-mortem case series: “43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. Interpretation: In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included.”

From the New England Journal of Medicine

Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults: “Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323 945 among those between the ages of 56 and 70 years and 1 128 391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1 183 066 and 3 638 522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. Conclusions: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial.”

From the MJA

Interpreting the effect of social restrictions on cases of COVID-19 using mobility data: “There appears to be three distinct types of societal reactions to social restrictions suggesting different degrees of economic shutdown; complete lockdown (Australia), partial lockdown with preserved workplace activity (Sweden) and minimal lockdown with preservation of both workplace and commercial activity (South Korea). The Australian graphs are the most orthodox and similar to most other countries with lockdowns, featuring large amplitude excursions (40–80%), with an axis of symmetry, suggesting people are not going to their workplaces and staying at home. Sweden is interesting in that there is also symmetry but with reduced workplace mobility decrement (20–40%), suggesting preservation of workplace activity. South Korea is intriguing as the amplitude is not only smallest (10%) but suggests a progressive loss of symmetry as time elapses. This mobility deficit is accounted for when considering the retail and recreation mobility data that depict a trend toward baseline commercial activity whilst maintaining low rates of new cases. Early social restrictions clearly reduce the spread of COVID-19.  Mobility data may help to guide policy that strikes the balance between social restrictions and new cases of COVID-19.”

Outcomes of COVID-19 patients admitted to Australian intensive care units during the early phase of the pandemic: The 204 patients who met inclusion criteria had a median age of 63 years (IQR, 53–72) and were predominantly male 140/204 (68.6%). Common comorbidities were obesity, diabetes, and chronic cardiac disease. No comorbidities were reported for 73/204 (35.8%). Returning international travellers were the most common source of infection (114/204, 55.9%). Median peak ICU bed occupancy was 14% (IQR, 9–16). Invasively ventilated patients (119/204, 58.3%,), compared to non-ventilated, had a longer median length of stay 16 days (IQR, 9–28) vs 3 days (IQR, 2–5) and higher ICU mortality 22% (95% CI, 15–31) vs 5% (95% CI, 1–12). Acute Physiology and Chronic Health Evaluation II (APACHE-II) score on day 1 (HR, 1.15; 95% CI, 1.09–1.21; P < 0.001) and chronic cardiac disease (HR, 3.38; 95% CI, 1.46–7.83; P = 0.004) were associated with higher ICU mortality. Conclusion: To the end of June 2020, patients admitted to Australian ICUs with COVID-19 requiring invasive ventilation had lower mortality and a longer length of stay than has been reported globally. These findings highlight the importance of ensuring adequate local ICU capacity, particularly with the recent increase in COVID-19 infections in Australia.”