ABSTRACT
Objective: Pregnancy is a risk factor for acute respiratory failure (ARF) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We hypothesised that SARS-CoV-2 viral load in the respiratory tract might be higher in pregnant intensive care unit (ICU) patients with ARF than in non-pregnant ICU patients with ARF as a consequence of immunological adaptation during pregnancy. Design: Single-centre, retrospective observational case- control study. Setting: Adult level 3 ICU in a French university hospital. Participants: Eligible participants were adults with ARF associated with coronavirus disease 2019 (COVID-19) pneumonia. Main outcome measure: The primary endpoint of the study was viral load in pregnant and non-pregnant patients. Results: 251 patients were included in the study, including 17 pregnant patients. Median gestational age at ICU admission amounted to 28 + 3/7 weeks (interquartile range [IQR], 26 + 1/7 to 31 + 5/7 weeks). Twelve patients (71%) had an emergency caesarean delivery due to maternal respiratory failure. Pregnancy was independently associated with higher viral load (-4.6 +/- 1.9 cycle threshold;P < 0.05). No clustering or over-represented mutations were noted regarding SARS-CoV-2 sequences of pregnant women. Emergency caesarean delivery was independently associated with a modest but significant improvement in arterial oxygenation, amounting to 32 +/- 12 mmHg in patients needing invasive mechanical ventilation. ICU mortality was significantly lower in pregnant patients (0 v 35%;P < 0.05). Age, Simplified Acute Physiology Score (SAPS) II score, and acute respiratory distress syndrome were independent risk factors for ICU mortality, while pregnancy status and virological variables were not. Conclusions: Viral load was substantially higher in pregnant ICU patients with COVID-19 and ARF compared with non-pregnant ICU patients with COVID-19 and ARF. Pregnancy was not independently associated with ICU mortality after adjustment for age and disease severity.
ABSTRACT
France was one of the first countries to be reached by the COVID-19 pandemic. Here, we analyse 196 SARS-Cov-2 genomes collected between Jan 24 and Mar 24 2020, and perform a phylodynamics analysis. In particular, we analyse the doubling time, reproduction number (Rt) and infection duration associated with the epidemic wave that was detected in incidence data starting from Feb 27. Different models suggest a slowing down of the epidemic in Mar, which would be consistent with the implementation of the national lock-down on Mar 17. The inferred distributions for the effective infection duration and Rt are in line with those estimated from contact tracing data. Finally, based on the available sequence data, we estimate that the French epidemic wave originated between mid-Jan and early Feb. Overall, this analysis shows the potential to use sequence genomic data to inform public health decisions in an epidemic crisis context and calls for further analyses with denser sampling.
ABSTRACT
Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.
ABSTRACT
While the SARS-CoV-2 genome has remained relatively stable since its emergence, genomic deletions are a frequently described evolutionary pattern of previous coronaviruses with significant impacts on outbreaks. This was the case in with both the SARS and MERS epidemics and has also recently been described with the massive surveillance of the SARS-CoV-2 genome since its emergence. During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) (n=229 sequences collected Feb-April 2020), two frameshifting deletions were detected in the open reading frame 6, starting at the same position (27267). While a 26-nucleotide deletion variant (D26) was only found in one nasopharyngeal sample in March 2020, the 34-nucleotide deletion variant D34) was found within a single geriatric hospital unit in 5/9 patients and one health care worker in April 2020. Phylogeny analysis strongly suggested a nosocomial transmission between patients for D34, with potential fecal transmission, as D34 was also identified in a stool sample. No difference in disease severity was observed within the patients hospitalized in the geriatric unit and infected with WT (n=4) or D34 (n=5). In vitro characterization of D26 and D34 revealed comparable replication kinetics with the wild-type (WT), but differential host immune responses. While interferon-stimulated genes were similarly upregulated after infection withWTand ORF6 deletion variants, the latter specifically induced overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including CCL2/MCP1, PTX3, and TNF, for which high plasma levels of these cytokines have been associated with severe Covid-19. Given the heterogeneous clinical manifestations of Covid-19 and the growing global prevelance of certain SARS-CoV-2 variants, our findings emphasize the need to monitor the occurrence of ORF6 deletions and assess their impact on the host immune response.