COVID-19 Research Round Up

The avalanche of COVID pre publications have slowed down into a trickle. I am highlighting a few pertinent articles here.
Guidelines/GuidanceOSHAGuidance on Preparing Workplaces for COVID-19.
Fiorino G et al. Clinician education and adoption of preventive measures for COVID-19: A survey of a convenience sample of general practitioners in Lombardy, Italy. Ann Intern Med 2020 Apr 15; [e-pub]. (https://doi.org/10.7326/M20-1447).  A survey that was sent in February and March 2020 to 450 Italian primary care physicians affiliated with a single hospital in Lombardy (the hardest hit region of Italy). Of 272 respondents (60% response rate) who were providing care to an estimated 400,000 patients, about half reported at least one known contact with a SARS-CoV-2 patient. Almost all had tried to prevent overcrowding in the office, and about 90% had modified their practice to include phone-based care or telemedicine.  Most had purchased their own personal protective equipment (PPE), less than half had received PPE from the Ministry of Health (the employer of Italian physicians), and less than 20% had provided PPE for use by waiting patients. About 40% reported that they themselves had experienced cough, fever, or gastrointestinal symptoms during the preceding 4 weeks; symptoms lasted for longer than 1 week in about half who were ill. Only 18 respondents were tested for SARS-CoV-2; only 2 tests were positive. The authors note that, when they wrote this report, 20 primary care physicians in the region had died of COVID-19.
.EpidemiologyPreliminary Estimate of Excess Mortality During the COVID-19 Outbreak —New York City, March 11–May 2, 2020. MMWR Morb Mortal Wkly Rep. ePub: 11 May 2020. During March 11–May 2, 2020, a total of 32,107 deaths were reported to DOHMH; of these deaths, 24,172 (95% confidence interval=22,980–25,364) were found to be in excess of the seasonal expected baseline. Included in the 24,172 deaths were 13,831 (57%) laboratory-confirmed COVID-19–associated deaths and 5,048 (21%) probable COVID-19–associated deaths, leaving 5,293 (22%) excess deaths that were not identified as either laboratory-confirmed or probable COVID-19–associated deaths. Counting only confirmed or probable COVID-19–associated deaths, however, likely underestimates the number of deaths attributable to the pandemic
Transmission/Infection Control Halfmann PJ, Hatta M, Chiba S, et al. Transmission of SARS-CoV-2 in Domestic Cats. New England Journal of Medicine. 2020;0(0):null. Three domestic cats were inoculated with SARS-CoV-2 on day 0. One day after inoculation, a cat with no previous SARS-CoV-2 infection was cohoused with each of the inoculated cats to assess whether transmission of the virus by direct contact would occur between the cats in each of the three pairs 5 days later, virus was detected in all three cats that were cohoused with the inoculated catspotential for SARS-CoV-2 transmission between family members in households with cats while living under “shelter-in-place” orderscats may be a silent intermediate host of SARS-CoV-2, because infected cats may not show any appreciable symptoms that might be recognized by their owners.CDC Guidance on Pets People with COVID-19 and in home isolation should be advised to restrict interaction with household animals, in addition to following other prevention measures to protect others from COVID-19. Specifically, while a person with COVID-19 is symptomatic, they should maintain separation from household animals as they would with other household members, and avoid direct contact with pets, including petting, snuggling, being kissed or licked, sleeping in the same location, and sharing food or bedding.
Hamner L, Dubbel P, Capron I, et al. High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice —Skagit County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. ePub: 12 May 2020.  Following a 2.5-hour choir practice attended by 61 persons, including a symptomatic index patient, 32 confirmed and20 probable secondary COVID-19 cases occurred (attack rate = 53.3% to 86.7%); three patients were hospitalized, and two died. Transmission was likely facilitated by close proximity (within 6 feet) during practice and augmented by the act of singing.
Clinical Syndrome Shekerdemian LS, Mahmood NR, Wolfe KK, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. Published online May 11, 2020. In this cross-sectional study of 46 North American PICUs, between March 14 and April 3, 2020, 48 children were admitted to 14 PICUs in the US and none in Canada. A total of 40 children (83%) had preexisting underlying medical conditions, 35 (73%) presented with respiratory symptoms, and 18 (38%) required invasive ventilation, and the hospital mortality rate was 4.2%.

Kawasaki/Toxic shock/MultisystemInflammatory syndrome in children1. Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020 Mar 28;395(10229): 1033-1034. . An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study -The Lancet. Accessed May 14, 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31103-X/fulltext. Thecases have in common overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters consistent with severe COVID-19 in children. Abdominal pain and gastrointestinal symptoms have been a common feature as has cardiac inflammation. Featuresappearto include high CRP, high ESR and high ferritin. In adults with COVID-19 disease, hyperinflammation or cytokine storm syndrome, as well as macrophage activation syndrome (MAS) and haemophagocytic lymphohistiocytosis (HLH) have been describedChildren are presenting with a picture of myocarditis with raised troponin and proBNP. Some have an appearance of their coronary arteries in keeping with Kawasaki Disease. Bergamo:30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease

Diagnostics Patel R, Babady E, Theel ES, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19. mBio. 2020;11(2). doi:10.1128/mBio.00722-20

Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and Renal Tropism of SARS-CoV-2. New England Journal of Medicine. 2020;0(0):null. RNA for angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and cathepsin L (CTSL) —RNA of genes that are considered to facilitate SARS-CoV-2 infection—is enriched in multiple kidney-cell types from fetal development through adulthood .This enrichment may facilitate SARS-CoV-2–associated kidney injury.Renaltropism is a potential explanation of commonly reported new clinical signs of kidney injury in patients with Covid-19,even in patients with SARS-CoV-2 infection who are not critically ill. Resultsindicate that SARS-CoV-2 has an organotropism beyond the respiratory tract, including the kidneys, liver, heart, and brain, and we speculate that organotropism influences the course of Covid-19 disease and, possibly, aggravates preexisting conditions.
Locatelli AG, Test ER, Vezzoli P, et al. Histologic features of long lasting chilblain-like lesions in a pediatric COVID-19 patient. Journal of the European Academy of Dermatology and Venereology. n/a(n/a). An adolescent in good health with occasional history of systemic symptoms preceding cutaneous lesions long lasting skin lesions several weeks after the first showings of the symptoms, concurrently with the positivity of the nasopharyngeal swab
Therapeutics Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine. 2020;382(19):1787-1799. Randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (SaO2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. Nobenefit was observed with lopinavir–ritonavir treatment beyond standard care.
Studies from New York: Geleris J et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19.N Engl J Med2020 May 7; [e-pub]. (https://doi.org/10.1056/NEJMoa2012410). Of 1376 patients assessed by Geleris, 811 (59%) received hydroxychloroquine, 86% of these starting within 48 hours of presentation. The patients who received hydroxychloroquine were more severely ill than those who did not according to multiple clinical and laboratory parameters. In an unadjusted analysis, patients who received hydroxychloroquine were significantly more likely to be intubated or die than those who did not (hazard ratio, 2.37; 95% confidence interval, 1.84–3.02). An adjusted analysis including the 811 hydroxychloroquine recipients and 274 nonrecipients with COVID-19 showed no significant difference in the composite endpoint of intubation or death (hazard ratio, 1.04; 95% CI, 0.82–1.32). Numerous sensitivity analyses had similar findings.
Rosenberg ES et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State.JAMA2020 May 11; [e-pub]. (https://doi.org/10.1001/jama.2020.8630) 1438 patients hospitalized with COVID-19 who received hydroxychloroquine alone (271 patients) or with azithromycin (735 patients), azithromycin alone (211 patients), or neither drug (221 patients). Overall in-hospital mortality was 20.3%. There was no significant difference in mortality across the groups. Cardiac arrest was significant more likely in patients receiving hydroxychloroquine with azithromycin
Xu X et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A2020 Apr 29; [e-pub]. (https://doi.org/10.1073/pnas.2005615117) Chinese investigators conducted a retrospective, uncontrolled study of 21 patients (average age, 57) with severe COVID-19symptoms (as defined by prespecified criteria) who received treatment with the IL-6 blocker tocilizumab (Actemra; approved in the U.S. to treat rheumatoid arthritis and juvenile idiopathic arthritis).  Within 24 hours of starting tocilizumab therapy, fevers and elevated C-reactive protein levels resolved, and levels of IL-6 and other proinflammatory cytokines declined. Use of supplemental oxygen dropped in 15 patients, oxygen saturation levels stabilized or improved in all patients, the 2 ventilated patients were weaned, and all patients subsequently were discharged aliv.e
Basic ScienceSingh T, Heston SM, Langel SN, et al. Lessons from COVID-19 in children: Key hypotheses to guide preventative and therapeutic strategies. Clinical Infectious Diseases. Published online May 8, 2020:ciaa547. doi:10.1093/cid/ciaa547 Deep dive into potential therapeutics from pediatric ‘relative immunity”concepts.
Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. Published online 2020. doi:10.12932/AP-200220-0773

Special PopulationsSantoli JM, Lindley MC, DeSilva MB, et al. Effects of the COVID-19 Pandemic on Routine Pediatric Vaccine Ordering and Administration —United States, 2020. MMWR Morb Mortal Wkly Rep. ePub: 8 May 2020. DOI:http://dx.doi.org/10.15585/mmwr.mm6919e2

Return to Play Phelan D, Kim JH, Chung EH. A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection.JAMA Cardiol.Published online May 13, 2020. doi:10.1001/jamacardio.2020.2136w

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