Severe acute respiratory syndrome (SARS) is the latest in a long list of emerging infectious diseases to gain the attention not only of the scientific community but also of the general public. SARS is characterised by symptoms that include a temperature over 38°C, dry cough, myalgia, and mild sore throat, which progresses to atypical pneumonia. The disease is unusual in its high morbidity and mortality rates; and it mimics and indeed rivals the 1918 influenza pandemic, which still stands as the worst pandemic in history. More disturbingly, SARS seems to transmit through direct contact and extreme infection-control measures are thus needed in affected areas. Although SARS currently has no absolutely confirmed cause, a first approximation of Koch’s postulates has been satisfied for a newly discovered virus within the family Coronaviridae. This newly identified virus has been designated SARS coronavirus (SARS-CoV). Coronaviruses are large enveloped viruses with a positive-sense RNA genome ranging in size from 27 to 30 kb, the largest of any of the RNA viruses. Clinically speaking, coronaviruses are usually associated with the common cold in human beings, but in animals the virus can lead to highly virulent respiratory, enteric, and neurological diseases as well as hepatitis. Human coronaviruses are usually difficult to culture in vitro, whereas most animal coronaviruses and SARS-CoV can be easily cultured in Vero E6 cells. Recently, in a Canadian collaborative tour de force, the Michael Smith Genome Sciences Centre in Vancouver, British Columbia, and the National Microbiology Laboratory in Winnipeg, Manitoba, were the first to obtain a full sequence of SARS-CoV. With 29 751 bases, the genome, denoted Tor-2, possesses a classic coronavirus complement of 11 open-reading frames, S and E glycoproteins, and the matrix, replicase, and nucleocapsid proteins. However, at the aminoacid level, SARS-CoV has minimum homology with any of the three classes of coronavirus; SARS-CoV thus lies in its own group. In today’s Lancet, YiJun Ruan and colleagues take the sequences of five SARS strains of known passage history in human beings and compare them with the Tor-2 sequence as well as other fully sequenced SARS-CoV strains from China and Vietnam. In addition to identifying small clusters of inherited mutations that are lineage-specific and can be used as molecular signatures to track transmission, the results suggest a remarkable genetic conservation of the virus since the outbreak was first documented in February, 2003. Although there are a handful of mutations between isolates, they may be due to adaption in culture. Previous experience with the evolution of influenza A virus shows that such “end-of-lineage” changes are due to mutations selected in laboratory culture. In Ruan’s study, most of the mutations in the SARS-CoV sequences probably represent adaption to Vero cells during propagation before sequencing. It can therefore be concluded that as the virus passes through human beings, SARS-CoV is maintaining its consensus genotype and is thus well adapted to the human host. This finding may indeed be a double-edged sword. SARS-CoV is not likely to change rapidly and thus may not readily mutate to a benign infection, as seen with most other infectious agents transmitted by direct contact and where patients’ mobility is crucial to facilitate transfer of disease. Any disease property that enhances transmission to new hosts will be the subject of positive evolutionary selective pressures. Experimental analysis of viral evolution shows that genomic stability in a specific host is a function of viral population size—passage of large populations results in increased replicative fitness and virulence due to the competitive selection of optimising mutations. By contrast, passage of limiting dosages results in decreased replicative fitness and attenuation due to the adventitious trapping of deleterious mutations. The hope with SARS-CoV is that it will

Chronic obstructive pulmonary disease (COPD) results from chronic inflammation, tissue injury, and aberrant repair processes in the respiratory airways. Acute viral and/or bacterial infections cause acute exacerbations. Rhinovirus (RV) infection is the most common viral cause of acute exacerbations in COPD, accounting for approximately 60% of viral acute exacerbations (1). Secondary bacterial infections frequently follow viral infection, resulting in more severe clinical illness with a greater reduction in FEV1 over FVC and greater length of hospitalization (2). In this issue of the Journal, Finney and colleagues (pp. 1496–1507) provide an important advance by demonstrating that a type A human RV (HRV) infection, HRV16, impairs phagocytosis of two important pathogens in COPD: nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (3). The HRV-associated phagocytic defect was demonstrated for both bacteria in the case of monocyte-derived macrophages (MDMs), but only for NTHi in the case of alveolar macrophages (AMs). Of note, the authors were able to demonstrate viral uptake by AMs challenged ex vivo, with cytoplasmic localization of virions. The phagocytic defect was reprised with a Toll-like receptor 3 (TLR3) agonist (polyinosinic:polycytidylic acid) and was a delayed response, requiring approximately 6 hours of HRV incubation. The authors also showed that HRV16 decreased proinflammatory cytokines in COPD MDMs challenged with NTHi. MDMs and AMs from subjects with COPD showed reduced phagocytosis to NTHi and S. pneumoniae (in the absence of HRV challenge) as compared with those obtained from healthy donors, and the degree of AM phagocytosis was correlated with MDM phagocytosis and with FEV1% predicted for both pathogens. Other models of the interaction between HRV and macrophages are of potential interest. HRV also induces replication-independent activation of TLR2 in mouse macrophages with production of proinflammatory cytokines (4). Conversely, HRV1B reduces CXCL8 (C-X-C motif chemokine ligand 8) production in response to NTHi, with reduced bacterial clearance and prolonged neutrophilic inflammation in mouse lungs (5). In this case, replication-independent viral responses induce degradation of IRAK-1 (IL-1 receptor–associated kinase 1), a key adaptor required for MyD88-dependent TLR signaling, inducing tolerance to bacterial stimuli in AMs. The data add to the range of viral infections that have been shown to alter macrophage phagocytosis of bacteria, including influenza A virus (6) and HIV-1 infection (7). Whether HRV can replicate in macrophages has been a subject of controversy. Viable virus was detected in MDMs, but only in one in a thousand cells (8). Detection of viable HRV16 in AMs infected ex vivo dropped to almost zero within 48 hours (9). In contrast, HRV16 RNA has been detected up to 10 days after infection of AMs. In the study by Finney and colleagues, a TLR3 agonist also inhibited phagocytosis, suggesting that a delayed pattern recognition receptor–mediated response could mediate the defect. Although cytoplasmic localization was described, it is of interest that there was no nuclear localization; therefore, the virologic mechanisms remain incompletely defined. In addition, the basis for a selective effect on COPD macrophages but not healthy macrophages is unclear. The authors previously described a systemic macrophage phagocytic COPD defect inMDMswhose development is independent of the unique environment of the COPD lung (10). This is in contrast to other reports that suggested phagocytic defects for NTHi in AMs, but not in MDMs (11). The authors suggest that this discrepancy may be ascribed to differences in the use of colony factors in MDM cultures. However, differences among assays are also likely to contribute, with some measuring uptake of heat-killed unopsonized bacteria (3, 10) and others measuring uptake of live bacteria with or without opsonization (11, 12). Although most studies have re

some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and COVID-19. In cows and pigs, Coronaviruses vary significantly in risk factor. Some can kill more than 30% of those infected, such as MERS-CoV, and some are relatively harmless, such as the common cold. Coronaviruses can cause colds with major symptoms, such as fever, and a sore throat from swollen adenoids. Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia) and bronchitis (either direct viral bronchitis or secondary bacterial bronchitis). The human coronavirus discovered in 2003, SARS-CoV, which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections. Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether.

If you have questions, ask your provider or a pharmacist. Antibiotics will not help with a cold. Antibiotics help with bacterial infections, not with viral infections such as colds. Most people who have a cold will feel better after a week or two. However, some people who get a cold may develop other illnesses, such as bronchitis or pneumonia. This is more common in people with weakened immune systems, asthma, or other respiratory conditions. Contact your provider if you or your child have symptoms that concern you, such as: Trouble breathing or fast breathing Dehydration Fever that lasts longer than 4 days Symptoms that last more than 10 days without improvement Symptoms, such as fever or cough, that improve but then return or worsen Worsening of chronic medical conditions Can the common cold be prevented? There is no vaccine to protect against the common cold. But you may be able to reduce your risk of getting or spreading a cold by: Washing your hands often with soap and water for at least 20 seconds. Avoiding touching your face, nose, or mouth with unwashed hands.