Experiences in the use of multiple doses of convalescent plasma in critically ill patients with COVID-19 (preprint)

At the beginning of the SARS-CoV-2 pandemic, transfusion of COVID-19 convalescent plasma (CCP) was considered as one of the possibilities to help severe patients to overcome COVID-19 disease. The use of CCP has been controversial as its effectiveness depends on many variables from the plasma donor and the COVID-19 patient, for example, time of convalescence or symptoms onset. This was a feasibility study assessing the safety of multiple doses of CCP in mechanically ventilated intubated patients with respiratory failure due to COVID-19. Thirty (30) patients with severe respiratory failure, in ICU, with invasive mechanical ventilation received up to 5 doses of 300 to 600 ml of CP on alternate days (0,2,4,6 and 8) until extubation, futility, or death. Nineteen patients received five doses, seven received four, and four had 2 or 3 doses. On day 28 of follow-up, 57% of patients recovered and were at home and the long-term mortality observed was 27%. The ten severe adverse events reported in the study were unrelated to CCP transfusion. This study suggests that transfusion of multiple doses of convalescent plasma (CP) is safe. This strategy may represent an option to use in new studies, given the potential benefit of CCP transfusions in the early stage of infection in unvaccinated populations and in settings where monoclonal antibodies or antivirals are contraindicated or not available.

Performance of a point of care test for detecting IgM and IgG antibodies against SARS-CoV-2 and seroprevalence in blood donors and health care workers in Panama (preprint)

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in eight months. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assays ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, participants with other confirmed infectious diseases, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test sensitivity and specificity as well as the kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement (87% (95% CI 67.0-96.3%)) was observed at [≥]15 days post-symptom onset. We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.

Early transmission dynamics, spread, and genomic characterization of SARS-CoV-2 in Panama. (preprint)

BackgroundWith more than 50000 accumulated cases, Panama has one of the highest incidences of SARS-CoV-2 in Central America, despite the fast implementation of disease control strategies. We investigated the early transmission patterns of the virus and the outcomes of mitigation measures in the country. MethodsWe collected information from epidemiological surveillance, including contact tracing, and genetic data from SARS-CoV-2 whole genomes, of the first five weeks of the outbreak. These data were used to estimate the exponential growth rate, doubling time and the time-varying effective reproductive number (Rt) using date of symptom onset in a Bayesian framework. The time of most recent ancestor for the introduced and circulating lineages was estimated by Bayesian analysis. FindingsA total of 4210 subjects were SARS-CoV-2 positive during the period evaluated, of them we sequenced 313 cases, detecting the circulation of 10 SARS-CoV-2 lineages. Whole genomes analysis identified the local transmission of one cryptic lineage as early as 2 weeks before it was detected by surveillance systems. Analysis of transmission dynamics showed that lockdown reduced Rt and increased the doubling time, however, these measures did not stop the circulation of this lineage in the country. InterpretationThese results demonstrate the value of epidemiological modeling and genome surveillance to assess mitigation strategies. At the same time, an active search for cryptic transmission clusters is crucial to interrupt local transmission of SARS-CoV-2 in a region. FundingMinistry of Health, Contribution from private donors and Secretaria Nacional de Ciencia y Tecnologia. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSIn May 2020, we searched for published studies in PubMed and web of Science related to genetic variability and dynamics of SARS-CoV-2 transmission in Latin America, and there was none. On July 2020, there was one study of this type on SARS-CoV-2 transmission in Brazil and none in Central America. We were particularly interested in SARS-CoV-2 cryptic transmission that could allow the virus spread through locals without being detected by respiratory health system surveillance, and no publication was reported. On July 2020, seven papers (five in preprint) were about SARS-CoV-2 cryptic transmission, one in China, another in UK and five in the US. None in Central America. All of them showed the importance of genomic surveillance to detect different lineage introductions, cryptic transmission and its role in early spread in a region or in health-care setting. Added value of this studyWe integrate data collected from tested individual during national surveillance of COVID19 suspected cases or contact of cases, as part of the National COVID19 Laboratory network. This data was used to estimate epidemiological parameters of the outbreak as well as the effect of mitigation measures on the epidemic dynamic. We sequence the whole genome of SARS-COV-2 of 7.4% of RT-PCR confirmed cases at the national level, and with phylogenetic analysis we identified SARS-CoV-2 lineages introduced in the country and estimate date of their introductions. Epidemiological and genetic data was compared and we observed the cryptic transmission of one introduced lineage and the rise of a local lineage that was not detected by the active contact tracing implemented by the health system surveillance. This cryptic lineage could explain the fact that early implementation measures decreased the transmission rate and the increased the doubling time, however they were not able to eliminate totally the virus spread. Implications of all the available evidenceThis is the first study that analyzed the epidemiology and transmission dynamics of the early COVID19 epidemic in a Central American country using both epidemiological and genomic surveillance. Our findings suggest that strict containment measures and movement restrictions in Panama might have contributed to decrease the early spread of the virus, but that cryptic local transmission allowed a continual basal virus diffusion that could explain, in part, the high incidence of cases in the country. More broadly, our findings are crucial to inform intervention policy in real-time, for countries in similar situations and the importance of constant monitoring of SARS-CoV-2 lineages to understand its transmission in a region.