Who brings the SARS-CoV-2 virus home and who spreads it around?

By Arpit C Swain

A child, a teenager and an adult enter a household… No, this is not the beginning of a joke. This is the beginning of a question for you. So, a child, a teenager and an adult enter a household, who do you think would be most likely to infect others in the household? If I were to venture a guess, I would say the child would be most likely to infect others in that household. The child has the most underdeveloped immune system among the three after all, and I have frequently heard the ‘must have been because of the daycare’ rhetoric from young parents who fall sick during the flu season. However, I would be wrong, at least if it’s the SARS-CoV-2 virus.

In their recent article, Christiaan H. van Dorp, a postdoctoral researcher at Columbia University Medical Center, and his colleagues find that adults are most likely to introduce an infection into a household, closely followed by teenagers, whereas children were only ~60% as likely as adults to introduce an infection into a household. They estimated that the rate at which an adult introduced an infection into a household was 0.0008 per day in mid-October 2020, which means that a group of 1200 adults infect one uninfected person every day.

The authors of this article used a prospective household study rather than a reactive household study. A reactive household study is not suitable to estimate how often an infection is introduced into a household as only households that are already infected are included in the study and the time of the infection is unknown. A prospective household study, in contrast, follows all participating households semi-passively during the at-risk period. In the Dutch study that Christiaan and team used for their analysis, more intensive follow-ups were performed upon notification of acute respiratory symptoms in the household.

The participating households were tracked for a maximum of 161 days. The team found that SARS-CoV-2 was introduced and established in 59 out of 307 households (~19%) between August 2020 and March 2021. The surge in hospitalization of hundreds of people in the same period closely followed the number of household infections (Figure 1). The peaks in hospital admissions (see the yellow dots) were always 1-2 weeks after the peak in the household infection rate.

Figure 1: The number of infections in the households is closely followed by the number of hospitalizations reported. The blue line is a measure of the infection rate of a household and the gray region around it is the variation in that rate.

The Netherlands was under lockdown during the period of the prospective household study. Christiaan and his colleagues’ analysis did not test whether children were less likely to introduce the infection into a household because of their limited interaction with the outside world during the lockdown. However, they tested whether the age of a person was a factor in how fast the virus was transmitted within a household upon its introduction into the household. They categorized the population into three different age groups: children (0-12 years old), adolescents (12-18 years old) and adults (above 18 years old). The team formulated a ‘full within household model’ where they tested all possible interactions between the three different age groups (see Figure 2). They found that once an infection had been introduced into a household, children were the primary age group that transmitted the infection within the household. The transmission rates due to adolescents and adults within a household were at most half of that of children, the rates for adolescents being marginally higher than that for adults (Figure 2).

Figure 2: All possibilities of transmission among the three age groups were tested in the full within household transmission model.

Using the full within household model again, Michiel van Boven, a researcher at University Medical Center Utrecht in the Netherlands, tested the effectiveness of a vaccine in controlling the spread of infection within a household. He assumed that a vaccine is ‘leaky’, which means that a vaccinated individual who contracts the virus would not be infected, however, can still spread the virus to others in the household. The simulations showed that vaccinating just the adults was effective in controlling the infection in the household. Vaccinating the adolescents, on top of the vaccination of adults, did not improve the control of infection. It is surprising that although adolescents are likely to introduce the infection into a household and also transmit it within the household, their vaccination does not improve the control of infection.

Christiaan and the team’s results from the prospective household study, therefore, shows that an adult brings the SARS-CoV-2 virus home which is then primarily transmitted within the household by children. Perhaps I was partially correct. A child would be most likely to infect the household, if it is already infected, otherwise it’s the adult who is most likely to infect the household.

Reviewed by: Christiaan van Dorp, Erin Cullen, Trang Nguyen, and Giulia Mezzadri

 

Why do COVID-19 patients have trouble breathing?

The COVID-19 pandemic has resulted in over 145 million positive cases and 3.1 million deaths globally (32 million and 570,000 in the USA, respectively), as reported on April 26, 2021. Approximately 15% of infected patients with SARS-CoV-2 die from respiratory failure, making it the leading cause of death in COVID-19 patients.

A research group at Columbia University led by Dr. Benjamin Izar identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions in the lungs of COVID19 patients. These findings were published in the prestigious journal Nature. The team performed single-nucleus RNA sequencing, which is a method for profiling gene expression in cells, of the lungs of 19 patients who died of COVID-19 and underwent rapid autopsy. The control group included seven control patients who underwent lung resection or biopsy in the pre-COVID-19 era (Figure 1).

Figure 1: An overview of the study design wherein single-nucleus RNA sequencing was used to characterize lungs of patients who died from COVID-19-related respiratory failure. A) The lung tissue was extracted for mRNA, a genetic sequencing of a gene. B) The mRNA sequence will be read by a computer system. C) The gene expression of cells in the lung of COVID-19 patients samples and control samples. PMI: post-mortem interval. snRNA-seq: single nucleus RNA sequencing. QC: quality control.

The lungs from individuals with COVID-19 were highly inflamed but had impaired T cell responses. The single-nucleus RNA sequencing showed significant differences in cell fractions between COVID-19 and control lungs both globally and within the immune and non-immune compartments. There was a reduction in the epithelial cell compartment, which are the surfaces of organs in the body and function as a protective barrier. There was also an increase in monocytes (i.e., white blood cells that are important for the adaptive immunity process) and macrophages (i.e., cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms), and a decrease in fibroblasts (i.e., cells that contribute to the formation of connective tissue) and neuronal cells. These observations were independent of donor sex. 

Monocyte/macrophage and epithelial cells were unique features of a SARS-CoV-2 infection compared to other viral and bacterial causes of pneumonia. The reduction in the epithelial cell compartment was due to the loss of both alveolar type II and type I cells. Alveolar type II cells repopulate the epithelium after injury, and provide important components of the innate immune system. Alveolar type II cells adopted an inflammation-associated transient progenitor cell state and failed to undergo full transition into alveolar type I cells, resulting in impaired lung regeneration. 

Myeloid cells (i.e., monocytes, macrophages, and dendritic cells) represented a major cellular constituent in COVID-19 lungs and were more prevalent as compared to control lungs. The authors found that the receptor tyrosine kinase that is important for coordinated clearance of dying/dead cells and subsequent anti-inflammatory regulation during tissue regeneration was downregulated. These data suggest that myeloid cells are a major source of dysregulated inflammation in COVID-19.

The authors also found significantly more fibroblasts in COVID-19 lungs than in control lungs. The degree of fibrosis correlated with disease duration, indicating that lung fibrosis increases over time in COVID-19. 

In this article, the authors mentioned the limitation of the study that they  analyzed lung tissues from patients who died of COVID-19, and therefore they only examined a subset of potential disease phenotypes. Based on the author’s observation, the rapid development of pulmonary fibrosis is likely to be relevant for patients who survive from severe COVID-19. This atlas may inform our understanding of long-term complications of COVID-19 survivors and provide an important resource for therapeutic development.

Read more about this article here: A molecular single-cell lung atlas of lethal COVID-19

Reviewed by: Molly Scott and Maaike Schilperoort

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