J Infect. Frontline Health Care Workers in Scotland and Their Families Are at Increased Risk of Hospitalization from COVID. The combination of a rapid response, extensive testing, quick results reporting, and comprehensive contact resulted in an impressive and rapid end to the outbreak. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. Investigators studied the incidence of thrombotic complications of all 184 ICU patients with COVID-19 pneumonia hospitalized at three Dutch academic medical centers. (Source: Carfi A, Bernabei R, Landi F, et al. They also provide guidance on when to use anticoagulants such as enoxaparin or warfarin. The authors do not state whether this was statistically significant, but it is possible it may have affected outcomes. They also tested healthcare workers purely based on symptoms. Their review process included searching for studies from more than 31 databases and preprint servers every day and assessing the risk of bias of the included studies. JAMA. Written by Henry C. Barry, MD, MS, on April 23, 2020. For this publication, they included 77 studies with 13,118 pregnant and recently pregnant women with COVID-19 and 83,486 nonpregnant women of reproductive age with COVID-19. Initial Report of Efficacy of Remdesivir for COVID-19 (ACTT). MMWR. Mean of estimated ratios of proportion of cases to proportion of population (range). They estimate that these measures reduced the number of confirmed cases in those six countries by more than 60 million, with a reduction of confirmed cases in the United States by 4.8 million and total cases by 60 million (assuming that many cases were asymptomatic or never confirmed). There was also a trend toward lower 14-day mortality in the remdesivir group (7.1% vs. 11.9%), but this was not statistically significant. This in vitro experiment demonstrates the significant potential for COVID-19 transmission in closed spaces. Vaccines and Related Biological Products Advisory Committee meeting; December 2020. https://www.fda.gov/media/144245/download). They excluded anyone known to have a prolonged QTc interval. Written by John Hickner, MD, MS, on June 26, 2020. Through contact tracing, they identified 400 close contacts. (Source: Sakurai A, Sasaki T, Kato S, et al. Not All Face Coverings Offer Similar Degrees of Protection. The intervention also decreased the number of gastrointestinal infections (21% vs. 25%, p < 0.001, NNT = 25) and the number of respiratory infections in a household member (44% vs. 49%, p < 0.001, NNT = 20). They randomized the patients to receive standard care (n = 100) or standard care plus an HIV medication, lopinavir/ritonavir (Kaletra; 400 mg/100 mg; n = 99), twice a day for 14 days. In the separate study of 77 infector-infectee pairs, based on epidemiological modeling and a mean incubation period of 5.2 days, they inferred that infectiousness starts 2.3 days before symptom onset with a peak infectiousness at 0.7 days prior to symptom onset. We have a report on a preprint server (not yet peer-reviewed) about the duration of post-COVID infection immunity. MMWR Morb Mortal Wkly Rep. 2020. http://dx.doi.org/10.15585/mmwr.mm6942e2). Benefit was smaller for patients not receiving mechanical ventilation at randomization and possibly for those receiving vasoactive agents at randomization. CMAJ. A study would need just more than 800 patients in each group, so hopefully this will be studied further. The authors do not report data on adverse events. Although there is no comparison with patients who have noncoronavirus respiratory infections, and anosmia is a feature of sinus infections, this seems much higher than would ordinarily be the case with other viral respiratory infections. A total of 2.0% of swabs from asymptomatic participants were PCR positive, compared with 18% from symptomatic participants. (Source: Cheng HY, Jian SW, Liu DP, Ng TC, Huang WT, Lin HH. In other words, the data that exist are of questionable reliability, and there are lots more data that have yet to be peer-reviewed. (Source: Wu Z, McGoogan JM. While the case fatality ratio (CFR) is higher in Italy than in China (7.2 % vs 2.3%), once stratified by age the CFRs are very similar within each age group up to age 70. The patients with COVID were slightly more likely to be obese and have dementia and diabetes mellitus, and those with seasonal influenza were slightly more likely to smoke, have cancer, cardiovascular disease, chronic lung disease, and use angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and statins. Similar findings were reported for American Indian and Alaskan Native populations in eight states (Arizona, 15.7% of hospitalizations vs. 4.0% of the population). Of the six patients in the placebo group who deteriorated on this scale, four were hospitalized, and one required mechanical ventilation, but at 30 days of follow-up none had died. One study reported that 27 (27%) children had redness or swelling of the lips or mucous membranes. It will take a larger, multicenter study to see whether this association is real. Most (81%) of the participants reported at least one adverse event within seven days of vaccination, and the overall rate was similar across all three doses. The primary outcome was clinical deterioration, defined as the development of dyspnea or need for hospitalization plus an oxygen saturation < 92% and was available for 84% of participants. They presented data from phase III randomized trials of the ChAdOx1 nCoV-19 vaccine in the United Kingdom and Brazil, and phase I/II clinical trials in the United Kingdom and South Africa. Food anaphylaxis is now the leading single cause of anaphylactic reactions treated in emergency departments in Westernized countries. 2020. https://doi.org/10.1056/NEJMoa2007764). For seven of the 10 sites, the estimated infections were 10 times greater than the reported number of cases. There are several plausible explanations for these findings: Children may be less likely than adults to be infective; asymptomatic children may have spread the virus more frequently and not been identified; or because of quarantine measures, children were less likely than adults to be exposed to COVID-19. PCR Sensitivity for Detection of COVID-19 Declines Rapidly over Time. The exposed students were asked to self-quarantine. One final comment. 2020 [published online April 15, 2020]. Written by John Hickner, MD, MS, on May 20, 2020. This is a cohort study from the United States, Canada, and Spain of 928 cancer patients with COVID-19 infection. They identified clusters of three or more cases linked temporally to the same infection venue. Several anonymous South African Twitter accounts gamed Twitter’s algorithms to get certain hashtags onto local trending lists. Meta-Analysis: COVID Testing Using Saliva Is as Accurate as Nasopharyngeal Swabs. NEJM. Written by Mark H. Ebell MD, MS, on May 7, 2020. Thirteen of 80 patients (16%) in the treatment group and 25 of 80 (31%) in the placebo group developed severe respiratory distress (relative risk = 0.52; 95% CI, 0.29 to 0.94; p = 0.03) If one eliminates from the analysis the six patients who reached the primary end point prior to receiving the infusion, the relative risk was 0.40 (95% CI, 0.20 to 0.81). The infection rate was much lower when the index case was asymptomatic or presymptomatic (0.7%) vs. symptomatic (18%). A subset of patients described in South Africa presented with a rapid onset of symptoms occurring within 45 mins. Natural History of Asymptomatic COVID-19 Infection in Cruise Ship Passengers. Patients were randomized in a 2:1 ratio to receive one or two doses of tocilizumab (n = 249) or placebo (n = 128) along with standard care. (3) Supply health workers with personal protective equipment and equip hospitals to care for a surge in severely ill patients. It is unclear whether children seeking care from otorhinolaryngologists are a reflection of the general population. Not surprisingly, most of the time patients tested positive at more than one site, regardless of who gathered the sample. 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. In the current study, 181 outpatients with PCR-confirmed COVID-19 who had been symptomatic for fewer than seven days were randomized to fluvoxamine or placebo in a double-blind manner. These authors reviewed the medical records of 850 consecutive patients hospitalized for COVID-19 over a two-week period in February 2020 in Wuhan, China. Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States [medRxiv preprint, not peer-reviewed February 7, 2021]. To estimate specificity, half of the samples were collected before the pandemic (good), whereas half of the samples were collected from patients not suspected to have COVID-19 (bad, as many cases are asymptomatic). 2020. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31173-9.pdf). This was a research design with biases that generally favor the intervention group, strengthening the findings of no differences in outcomes. The report does not say what proportion of patients had developed cellular immunity. To prevent a pandemic, if 100% of U.S. residents received the vaccine, vaccine efficacy would need to be 60%; if 75% of U.S. residents received the vaccine, it would need to be 70% effective in preventing individual infection; and if 60% of U.S. residents received the vaccine, it would need to be 80% effective to prevent a pandemic. Post–FDA EUA, despite very strong safety signals in both phase 3 trials, reports of possible allergic reactions have raised public concern. Close contacts of 100 confirmed COVID-19 patients in Taiwan were identified and followed to ascertain what proportion of them became infected with the coronavirus. JAMA Intern Med. HB remains highly or moderately endemic in the Far East, the Middle East, Africa, South America, Eastern Europe and Central Asia, with carrier rates of 2% to 20% in the general population. EUA application was submitted to FDA February 4, 2021.) ; Henry Ford COVID-19 Task Force. (Source: Kuderer NM, Choueiri TK, Shah DP, et. Dippenaar J, Naidoo S. Allergic reactions and anaphylaxis during anaesthesia. All were treated with antiplatelet therapy, one with tissue plasminogen activator, and four with clot retrieval. During these two weeks, they had visited 5,880 homes with 31,164 persons (222 subsequently tested positive for COVID-19). Overall, pregnant women were less likely to have fever (OR 0.43, 95% CI 0.22 to 0.85, but high heterogeneity) and myalgias (OR 0.48, 95% CI 0.45 to 0.51; no heterogeneity). The researchers report significant heterogeneity in the magnitude of the response, but generally found that the participants who were initially symptomatic had 50% higher levels than those who were asymptomatic. Mortality is not reported, and adverse events were more common in the HCQ group. Antibodies Persist for Four Months after Infection; Infection Fatality Ratio 0.3%, Much Higher in Older Patients. The mean age was 57 years, and 63% were men. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Lancet , 397 ( 2020 ) , pp. For all of the tests, sensitivity was unacceptably low for IgG and IgM until at least three weeks after symptom onset. However, after publication of that report and more experience with the Pfizer BioNTech COVID-19 vaccine, the CDC revised this estimate downward on January 27, 2021, to five per 1,000,000 doses, which is one in 200,000 doses. This study provides strong evidence that a second COVID-19 infection is highly unlikely within six months of the original infection. A single episode of a serious hypersensitivity reaction occurred, but it was not anaphylaxis. Written by Mark H. Ebell MD, MS, on July 6, 2020. The overall case fatality rate of laboratory confirmed cases was 2.3% and was 14.8% for those older than 80 years. The onset was within 15 minutes of vaccine administration in nine individuals and after 30 minutes in one case. In the real world, clinicians seeing a high-risk patient with symptoms and a COVID exposure are more likely to apply data from the main analysis and not this last one. Face Mask Mandate Slowed Spread of COVID-19 Transmission in Kansas Counties. A living WHO guideline on drugs for covid-19. https://jamanetwork.com/journals/jama/fullarticle/2766182). In this prepublication release from the American Journal of Gastroenterology, the authors report data from an online survey. Overall, 96 children were included in these studies, 38 (40%) were black, 81 (84%) had lab-confirmed COVID-19, and 33 (34%) also met criteria for Kawasaki disease. This study compared daily changes in COVID-19 cases in eight Iowa counties bordering Illinois (where no stay-at-home order was in place) with seven Illinois counties bordering Iowa (where stay-at-home orders were in place). Of the 113 who were initially weakly positive or negative, 64 returned a median of 13 days later, and at that time 57 were strongly positive, four were weakly positive, and three were negative at follow-up (the PCR for these three was self-reported, a possible source of error). If so, this report has significant implications as the United States opens restaurants and other business venues requiring close physical proximity and ventilation. 2020. https://www.cmaj.ca/content/early/2020/11/23/cmaj.202065.long). (Source: Kucirka LM, Lauer SA, Laeyendecker O, et al. The clear winner was the commercially made, fitted N95 masks that, compared with the unmasked controls, transmitted less than 0.1% of the droplets. The trial was stopped early because of publication of the positive results from the RECOVERY trial on June 16, 2020, because the investigators believed that there was no longer clinical equipoise and that hydrocortisone should not be withheld from critically ill COVID-19 patients. Based on a network meta-analysis of four randomized trials, the WHO guideline recommends remdesivir only for patients hospitalized with nonsevere COVID-19. 2020 [published online April 13, 2020]. The study originally planned to enroll 150 patients, but the data-monitoring board stopped enrollment after 129 patients due to excess deaths in the patients randomized to receive tocilizumab. 2020;3(6):e2011335. All had oxygen saturation greater than 93% or PaO2/FIO2 ratio > 300. Written by Henry C. Barry, MD, MS, on October 4, 2020. 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2019375). authorized a second Covid-19 vaccine for emergency use, clearing the way for millions more Americans to be immunized next week. On the other hand, two studies of cotton mask wearers suggest moderate protection against inhalation of infectious-sized particles. (Source: Van Dyke ME, Tia M, Rogers TM, et al. 2021;70(2):46-51.). Spanish RCT of Hydroxychloroquine for Patients with Early, Nonsevere COVID-19 Finds No Benefit. JAMA Intern Med. N Engl J Med. Around the world, more than 100 candidate vaccines against SARS-CoV-2 are in various stages of development and testing. Written by Mark H. Ebell, MD, MS, on July 27, 2020. Time course of a second outbreak of COVID-19 in Beijing, China, June-July 2020 [published online August 24, 2020]. 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2016638). This study enrolled 491 nonhospitalized patients with confirmed or probable COVID-19 who were enrolled online. Although there is no comparison with non-COVID-19 patients, the authors argue that these rates are higher than with other respiratory infections such as influenza. Three recent papers report data from medical record audits of children hospitalized in New York, France, and England. The final assessment of the authors is that no difference occurred in outcomes between 5 and 10 days, so 5 days should be considered, especially if supplies are limited. Euro Surveill. Indoor transmission of SARS-CoV-2 [published online April 7, 2020]. No difference occurred between groups with regard to 28-day mortality (26.8% HCQ vs. 25.0% usual care, rate ratio [RR] 1.09, 95% CI 0.96 to 1.23). Twenty-six athletes (15 males, 11 females) agreed to participate. JAMA Intern Med. It includes 44 studies of transmission within households and 10 studies of transmission within families (where not all members of the family lived in the same household). Fluvoxamine is an SSRI primarily used to treat obsessive-compulsive disorder. Because patients prescribed ACEIs or ARBs are more likely to also have serious comorbid conditions, the researchers performed a propensity-weighted analysis to attempt to adjust for known confounders. Thromb Res. Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing [published online September 16, 2020]. Strongly positive patients (IgG titer > 1:320) were referred for donation of sera, whereas those who were weakly positive or who were initially negative for IgG returned at least a week later for retesting. Spread during the presymptomatic and early symptom phase, such as with the influenza virus, could make it difficult to institute effective quarantine procedures. The model was generally best at ruling out mortality than ruling it in, as summarized in Table 2 in the source cited here. 2021;384(1):20-30.). The analysis used a propensity score-matched approach to adjust for comorbidities, tobacco use, medications, and laboratory results. Multisystem inflammatory syndrome in U.S. children and adolescents [published online June 29, 2020]. 2020;3(9):e2019722.). Adding this inclusion criterion may have limited the number of potential studies compared with looking at prevalence and secondary infection alone. (Source: Toscano G, Palmerini F, Ravaglia S, et al. (Written by Mark H. Ebell MD, MS, on February 13, 2021. They identified nine clinical trials, and seven agreed to share data with the REACT team for meta-analysis. N Engl J Med. (Source: Cao B, Wang Y, Wen D, et al. Lancet. COVID-19 Hospitalization Rates Higher for Hispanic and Black Children Than for White Children. In a randomized trial, the known and unknown factors associated with the outcome of interest are evenly distributed between the intervention groups. They identified patients with gastrointestinal (GI) symptoms (“cases”) and matched them to the next admitted patient who had no GI symptoms (“controls”). Written by John Hickner, MD, MS, on September 4, 2020. Ann Intern Med. The National Institute of Allergy and Infectious Diseases (NIAID) released initial results (not peer reviewed, full data not yet available) for the Adaptive COVID-19 Treatment Trial. The prevalence of antibodies to SARS-CoV-2 ranged from 1.0% in the San Francisco Bay area to 6.9% in New York City. Written by John Hickner, MD, MS, on June 17, 2020. 2020. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767980). Prior to this study, however, there had not been any randomized trials of mask wearing to protect wearers in the community from COVID-19 infection. BMJ. Written by John Hickner, MD, MS, on September 14, 2020. This is their third update, which replaces the one issued in November 2020. The Resuscitation Council of Southern Africa. The study, the Adaptive Covid-19 Treatment Trial (ACTT-1), took place in 60 different sites in the United States, Germany, Denmark, the United Kingdom, Greece, Korea, Mexico, Spain, and Japan. Because this is a lab-based study, it is unclear whether this translates to real-world immunity. The outcome, neutralizing antibody generation as determined by a 50% plaque reduction neutralization assay, demonstrated the vaccine to be as effective against the mutant strains. The mortality results were adjusted for age, burden of chronic disease using the Charlson Comorbidity Index, public insurance status, residence in a low-income area, and obesity, factors all associated with increased odds of hospital admission. Stay tuned for the definitive studies on the effectiveness and safety of this vaccine. JAMA Network Open. At least it does appear to be safe. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593). This retrospective cohort study determined the incidence of COVID-19 in those with and without vitamin D deficiency, as measured within the prior year. The hospitalization rate was much higher for Hispanic and Black children (16.4 and 10.5 per 100,000, respectively) compared with non-Hispanic White children (2.1 per 100,000). is a voluntary co-ordinating body whose primary aim is to foster and co-ordinate resuscitation training and practice Written by Henry C. Barry, MD, MS, on April 23, 2020. The health care workers were subsequently tested for SARS-CoV-2 infection every two months and were asked whether they developed COVID-19 symptoms. Researchers conducted an open-label randomized trial in one of 16 designated COVID-19 treatment centers in China. (Source: The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Baricitinib plus remdesivir for hospitalized adults with Covid-19 [published online December 11, 2020; updated January 5, 2021]. 2020;370;m3379.). The most reported predictors of severe prognosis (deterioration to severe or critical disease, prolonged hospitalization, or death) in patients with COVID-19 included age, sex, computed tomography findings, C-reactive protein, lactic dehydrogenase, and lymphopenia. Updated February 22, 2021. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/).
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