Latest in Pulmonary Newslungcare2019-02-15T07:28:32-05:00
Frontline Health Care Workers in Scotland and Their Families Are at Increased Risk of Hospitalization from COVID
These researchers identified 158,445 Scottish health care workers between 18 and 65 years of age who were employed by the National Health Service. They used Scottish employment databases to create linkages to other health-related databases and to identify members of their households (n = 229,905). Additionally, the researchers used these same databases to identify people from the general population. They mined the databases to identify hospitalizations for COVID between March 1, 2020 (when cases of COVID were first identified in Scotland), and June 6, 2020. Among the health care workers, 90,733 (57.3%) had direct patient contact (they used the term “patient-facing”), and 79% were women. During the study period, they identified 6,346 hospitalizations for COVID, 2,097 of which occurred in people between 18 and 65 years of age. Of these, 1,737 (82.8%) occurred in the general population, and health care workers and their household members accounted for 243 (11.6%) and 117 (5.6%), respectively. After adjusting for age, sex, ethnicity, socioeconomic factors, and comorbidities, the overall risk of hospitalization for all health care workers and their households was similar to that of the general population. However, among patient-facing health care workers, while the numbers were small, the risk of hospitalization was much higher (hazard ratio 3.30, 95% CI, 2.13 to 5.13) as was the risk for their household members (hazard ratio 1.79, 95% CI, 1.10 to 2.91). Combining these data with the data in the Research Brief posted on October 23, 2020, summarizing the CDC’s October report on excess mortality attributed to COVID19 (http://dx.doi.org/10.15585/mmwr.mm6942e2) illustrates the risk to health care workers, their families, and the public. It’s hard to imagine where any profit could be gained from naming COVID as a cause of death.
Written by Henry C. Barry, MD, MS, on November 1, 2020. (Source: Shah ASV, Wood R, Gribben C, et al. Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study. BMJ. 2020;371:m3582.)
Convalescent Plasma Does Not Reduce Worsening nor All-Cause Mortality in Patients Hospitalized with Moderate COVID in India (PLACID Trial)
n this open-label phase II trial from 39 hospitals in India, the researchers randomized patients to standard care (n = 229) or standard care plus convalescent plasma (n = 235). The patients had all been hospitalized with moderate illness (PaO2/FiO2 ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24 per minute with oxygen saturation 93% or less on room air). To be eligible, there also had to be a matched plasma donor (adults with a previous PCR-confirmed symptomatic bout with COVID). The staff administered the convalescent plasma as two infusions administered 24 hours apart. Standard care, a kitchen sink of protocols that appeared to be unique to each hospital, could include hydroxychloroquine, oseltamivir, remdesivir, lopinavir/ritonavir, broad spectrum antibiotics, steroids, tocilizumab, and good supportive care. About two-thirds of the patients had preexisting comorbidities, and three-quarters were male. Most (91%) had dyspnea at baseline, and two-thirds had chest radiography with bilateral “patchy shadows.” After 28 days of follow-up, 41 (18%) of control patients died or had progression to severe disease compared with 44 (19%) of those receiving convalescent plasma. One potential limitation is that of the samples of convalescent plasma tested, 29% had no detectable neutralizing antibodies.
Source: Written by Henry C. Barry, MD, MS, on October 27, 2020. https://www.aafp.org/journals/afp/content/covid-briefs.html (Source: Agarwal A, Mukherjee A, Kumar G, et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial [PLACID Trial]. BMJ. 2020;371:m3939.)
Antibodies Persist for Four Months after Infection; Infection Fatality Ratio 0.3%, Much Higher in Older Patients.
This Icelandic study measured a variety of IgG and IgM antibodies to SARS-CoV-2 in six groups of Icelanders who had either never been tested or had tested negative and in two groups of Icelanders who had tested positive and had recovered. They weighted the sample by age and sex to estimate the number of Icelanders who had been infected and used that to estimate the infection fatality ratio (deaths/[symptomatic + asymptomatic positives]) and case fatality ratio (deaths/symptomatic positives). Among patients who had experienced a symptomatic infection, IgG antibody levels remained stable over a four-month period, which is encouraging in terms of at least medium-term immunity. Those who smoked and those taking anti-inflammatory medications had lower antibody levels, although it is not clear whether this difference is clinically significant. This was not the case for IgM and IgA antibodies, which is what you would expect. They also estimate that the infection fatality ratio was 0.3% (95% CI, 0.2% to 0.6%), and the case fatality ratio was 0.6% (95% CI, 0.3% to 1.0%). The infection fatality ratio was 0.1% (95% CI, 0.0% to 0.3%) in people 70 years or younger and 4.4% in those older than 70 years (95% CI, 1.9% to 8.4%).
Source: Gudbjartsson DF, Norddahl GL, Melsted P, et al. Humoral immune response to SARS-CoV-2 in Iceland [published online September 1, 2020]. N Engl J Med. 2020. DOI: 10.1056/NEJMoa2026116).
Meta-analysis of Seven RCTs Confirms That Systemic Corticosteroids Reduce 28-Day COVID-19 Mortality
The World Health Organization has created a Rapid Evidence Appraisal for COVID-19 Therapies (REACT) working group to perform an ongoing series of meta-analyses. This meta-analysis did a careful search of clinical trial registries to identify all ongoing or completed studies comparing a systemic corticosteroid with placebo or usual care in patients who were critically ill with COVID-19. Trials that included patients with mild or moderate disease or that had not recruited patients were excluded. They identified nine clinical trials, and seven agreed to share data with the REACT team for meta-analysis. Trials were done in six European countries, the United States, Canada, Brazil, New Zealand, Australia, and China. The median age of participants was 60 years, 29% were women, and all but one study required ICU admission. Data from the large UK RECOVERY trial was limited to the subgroup of patients who were mechanically ventilated. Risk of bias was assessed as low using the Cochrane Risk of Bias Tool for six of seven trials. In total, 678 patients were randomized to a corticosteroid and 1,025 to usual care or placebo. There was good consistency across trials in their results, with the I2 of 16% (that means that only 16% of the identified variance was between studies and that 84% was within studies). Corticosteroids significantly reduced mortality (odds ratio 0.66, 95% CI 0.53 to 0.82; risk ratio 0.80, 95% CI 0.70 to 0.91). I think risk ratios are more appropriate because odds ratios are only an approximation of relative risk and are most reliable when outcomes are rare (not the case here). Given a 41.4% mortality rate in the usual care/placebo group, applying the risk ratio of 0.80 yields a 20% mortality reduction to 33.2%, which corresponds to a number needed to treat to prevent one death of 12. They found no difference in outcomes by age, dose of steroid, or duration of illness prior to enrollment. Benefit was smaller for patients not receiving mechanical ventilation at randomization and possibly for those receiving vasoactive agents at randomization. This provides support for use of low-dose corticosteroids in critically ill patients but should not be applied to outpatients or patients not requiring supplemental oxygen.
Written by Mark H. Ebell MD, MS, on September 3, 2020. (Source: The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis [published online September 2, 2020]. JAMA. 2020.
Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19
Introduction: To compare outcomes in patients hospitalized with coronavirus (COVID-19) receiving famotidine therapy with those not receiving famotidine.
Methods: Retrospective, propensity-matched observational study of consecutive COVID-19-positive patients between February 24, 2020, and May 13, 2020.
Results: Of 878 patients in the analysis, 83 (9.5%) received famotidine. In comparison to patients not treated with famotidine, patients treated with famotidine were younger (63.5 ± 15.0 vs 67.5 ± 15.8 years, P = 0.021), but did not differ with respect to baseline demographics or preexisting comorbidities. Use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio 0.37, 95% confidence interval 0.16-0.86, P = 0.021) and combined death or intubation (odds ratio 0.47, 95% confidence interval 0.23-0.96, P = 0.040). Propensity score matching to adjust for age difference between groups did not alter the effect on either outcome. In addition, patients receiving famotidine displayed lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs 12.7 mg/dL, P = 0.002), lower median procalcitonin levels (0.16 vs 0.30 ng/mL, P = 0.004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs 964.0 ng/mL, P = 0.076). Logistic regression analysis demonstrated that famotidine was an independent predictor of both lower mortality and combined death/intubation, whereas older age, body mass index >30 kg/m, chronic kidney disease, National Early Warning Score, and higher neutrophil-lymphocyte ratio were all predictors of both adverse outcomes.
Discussion: Famotidine use in hospitalized patients with COVID-19 is associated with a lower risk of mortality, lower risk of combined outcome of mortality and intubation, and lower levels of serum markers for severe disease in hospitalized patients with COVID-19.
Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses
Objectives: As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical. Study design: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital (MGH) were offered enrollment in the MGH Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.
A total of 192 children (mean age 10.2 +/- 7 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met criteria for MIS-C. Only 25 (51%) of children with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were non-specific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower ACE2 expression (P=0.004). IgM and IgG to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein were increased in severe MIS-C (P<0.001), with dysregulated humoral responses observed.
Conclusion: This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms, and immune dysregulation is implicated in severe post-infectious MIS-C.
Source: Yonker LM, Neilan AM, Bartsch Y, Patel AB, Regan J, Arya P, Gootkind E, Park G, Hardcastle M, St. John A, Appleman L, Chiu ML, Fialkowski A, De la Flor D, Lima R, Bordt EA, Yockey LJ, D’Avino P, Fischinger S, Shui JE, Lerou PH, Bonventre JV, Yu XG, Ryan ET, Bassett IV, Irimia D, Edlow AG, Alter G, Li JZ, Fasano A, Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses, The Journal of Pediatrics (2020), doi: https://doi.org/10.1016/ j.jpeds.2020.08.037.
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