ABSTRACT
A surge in Covid-19 cases in Mongolia in March 2021 resulted in a government-mandated shutdown. This shutdown was relaxed in May 2021 as case numbers decreased and nationwide vaccination rates using Sinopharm, Covishield/AstraZeneca, Sputnik V, and Pfizer/BioNTech vaccines exceeded 50% of the population. Case rates increased again in early June 2021 in both vaccinated and non-vaccinated individuals. To determine whether the surge was due to the emergence of Delta or another variant, or vaccine failure, a rapid, opportunistic investigation was conducted that comprised virus sequence analysis of nasal swab samples from breakthrough cases and antibody assays of plasma from healthy vaccinees. More than 90% of breakthrough infections during the second case surge were due to the Alpha variant. Spike protein ELISA and SARS-CoV-2 neutralization assays data revealed large differences in plasma titers of antibodies to SARS-CoV-2, with mRNA vaccines eliciting higher titers than adenovirus-vectored or killed virus vaccines.
ABSTRACT
BackgroundAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited. ObjectiveTo evaluate the clinical efficacy and safety of convalescent plasma among adults hospitalized with severe and critical COVID-19. DesignRandomized, double-blind, controlled, multicenter, phase 2 trial conducted from April 21st to November 27th, 2020. SettingFive hospitals in New York City (NY, USA) and Rio de Janeiro (Brazil). ParticipantsHospitalized patients aged [≥]18 years with laboratory-confirmed COVID-19, infiltrates on chest imaging and oxygen saturation [≤] 94% on room air or requirement for supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. InterventionParticipants were randomized 2:1 to a single transfusion of either 1 unit of convalescent or normal control plasma. MeasurementsThe primary outcome was clinical status at 28 days, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population. ResultsOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to normal control plasma. At 28 days, no significant improvement in clinical status was observed in participants randomized to convalescent plasma (with an odds ratio (OR) of a 1-point improvement in the scale: 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples (n=40) from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected. Serious adverse events occurred in 39/147 (27%) participants who received convalescent plasma and 26/72 (36%) participants who received control plasma. LimitationsSome participants did not receive high-titer convalescent plasma. ConclusionIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in 28 days clinical status. The significant reduction in mortality associated with convalescent plasma, however, may warrant further evaluation. RegistrationClinicalTrials.gov, NCT04359810 FundingAmazon Foundation Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT04359810
ABSTRACT
Serodiagnosis of SARS-CoV-2 infection is impeded by immunological cross-reactivity to the human coronaviruses (HCoV) SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, 229E, HKU1, and NL63. Here we report the identification of humoral immune responses to SARS-CoV-2 and other HCoV peptides that can be used to detect asymptomatic, mild and, severe SARS-CoV-2 infections, and may enable the discovery of biomarkers for immunity following infection or vaccination.
ABSTRACT
<p><b>BACKGROUND</b>Several coronaviruses establish persistent infections in vitro and in vivo, however it is unknown whether persistence is a feature of the severe acute respiratory syndrome coronavirus (SARS-CoV) life cycle. This study was conducted to investigate viral persistence.</p><p><b>METHODS</b>We inoculated confluent monolayers of Vero cells with SARS-CoV at a multiplicity of infection of 0.1 TCID50 and passaged the remaining cells every 4 to 8 days for a total of 11 passages. Virus was titrated at each passage by limited dilution assay and nucleocapsid antigen was detected by Western blot and immunofluoresence assays. The presence of viral particles in passage 11 cells was assessed by electron microscopy. Changes in viral genomic sequences during persistent infection were examined by DNA sequencing.</p><p><b>RESULTS</b>Cytopathic effect was extensive after initial inoculation but diminished with serial passages. Infectious virus was detected after each passage and viral growth curves were identical for parental virus stock and virus obtained from passage 11 cells. Nucleocapsid antigen was detected in the majority of cells after initial inoculation but in only 10%-40% of cells at passages 2-11. Electron microscopy confirmed the presence of viral particles in passage 11 cells. Sequence analysis at passage 11 revealed fixed mutations in the spike (S) gene and ORFs 7a-8b but not in the nucleocapsid (N) gene.</p><p><b>CONCLUSIONS</b>SARS-CoV can establish a persistent infection in vitro. The mechanism for viral persistence is consistent with the formation of a carrier culture whereby a limited number of cells are infected with each round of virus replication and release. Persistence is associated with selected mutations in the SARS-CoV genome. This model may provide insight into SARS-related lung pathology and mechanisms by which humans and animals can serve as reservoirs for infection.</p>
