COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina (preprint)

In December 2019, a novel illness called coronavirus disease 2019 (COVID 19) was described in China and became pandemic in a few months. The first case was detected in Argentina on March 3, 2020. A multicentre prospective observational cohort study on hospitalized patients with COVID 19 was conducted in 4 hospitals in San Isidro district from March 1, 2020 to October 31. Data was obtained by the attendant physician. 668 patients were included, the median age was 54 years, and 42.7% were female. Male sex and older age were associated with COVID 19 disease and more strongly with severity. Most frequent symptoms were fever and cough followed by dyspnoea, myalgia, odynophagia, headache, anosmia, and diarrhoea. Nonsevere patients had more upper respiratory symptoms while severe patients had mainly lower respiratory symptoms on admission. Most common comorbidities were arterial hypertension, diabetes, and cardiovascular disease. A great proportion of patients had normal thorax X ray and ground-glass opacity in tomography. In severe patients, radiography and tomography had a predominant ground glass pattern, but normal radiography and tomography on presentation were present in 22% and 5.9%, respectively. The absence of fever and normal radiology on admission neither excluded the disease nor further severity. PCR elevation was related with COVID 19 disease and with severity, while lymphopenia was more related with the disease and leukocytosis and thrombocytopenia with severity. 8, 4% of patients were health care workers. The mortality rate was 12.4%, 32.7% in severe patients and 61.2% in ventilated patients. Mortality was higher in the public hospital, probably associated with patients with older age and more comorbidities. All these observations can contribute to the knowledge of this disease in terms of diagnosis and prognosis.

Prevention of severe COVID-19 in the elderly by early high-titer plasma (preprint)

BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression. MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate [≥]30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible. Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%. A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed. ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives. Funded by The Bill & Melinda Gates Foundation and The Fundacion INFANT Pandemic Fund. Registered in the Direccion de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163). All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

Modeling the frequency and number of persons to test to detect and control COVID-19 outbreaks in congregate settings (preprint)

BackgroundCongregate settings are at risk for coronavirus disease 2019 (COVID-19) outbreaks. Diagnostic testing can be used as a tool in these settings to identify outbreaks and to control transmission. MethodsWe used transmission modeling to estimate the minimum number of persons to test and the optimal frequency to detect small outbreaks of COVID-19 in a congregate facility. We also estimated the frequency of testing needed to interrupt transmission within a facility. ResultsThe number of people to test and frequency of testing needed depended on turnaround time, facility size, and test characteristics. Parameters are calculated for a variety of scenarios. In a facility of 100 people, 26 randomly selected individuals would need to be tested at least every 6 days to identify a true underlying prevalence of at least 5%, with test sensitivity of 85%, and greater than 95% outbreak detection sensitivity. Disease transmission could be interrupted with universal, facility-wide testing with rapid turnaround every three days. ConclusionsTesting a subset of individuals in congregate settings can improve early detection of small outbreaks of COVID-19. Frequent universal diagnostic testing can be used to interrupt transmission within a facility, but its efficacy is reliant on rapid turnaround of results for isolation of infected individuals.