The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. The pathogen was traced to the Huanan Seafood Wholesale Market. The dynamics of method of transmission and and infection dynamics of disease have helped shape some of the measures taken to limit the spread of disease. Some of these seem to be working and some have caused catastrophes in different parts of the world. Some facts taken from a study “Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia” Published in the March 26, 2020 N Engl J Med 2020; 382:1199-1207 are given below.
Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).
There was human to human transmission, respiratory droplets were involved in the transmission, physical contact with mucosal surfaces could result in transmission of the virus to hands and then could be transmitted to any surface touched by an infected person. The transmission could take place unless controlled by hand washing and antiseptic cleaning of the surfaces, for a period of 7 days. Hence a symptomatic patient needs to be isolated for 7 days or until tests are negative for the presence of the virus. Taking into account that an asymptomatic person can also transmit the disease and the incubation period is 14 days such a person needs to be isolated for 14 days. Families can be isolated in their homes or group accommodation. It would however be advisable to isolate the elderly and vulnerable separately in a room of their own. As the virus is not transmitted by food, drink and cooking utensils meals and food can be shared. If an asymptomatic patient becomes symptomatic then they need to isolate for an additional days.
Have we had similar viruses in the past? COVID 19 was rapidly shown to be caused by a novel coronavirus that is structurally related to the virus that causes severe acute respiratory syndrome (SARS). There have been two preceding instances of emergence of coronavirus disease in the past 18 years — SARS (2002 and 2003) and Middle East respiratory syndrome (MERS) (2012 to the present) — the Covid-19 outbreak has posed critical challenges for the public health, research, and medical communities. Two pandemics of influenza occured in 1957 and 1968. Spanish flu occured in 1917.
How often have we dealt with the corona virus in the past? Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2, have been responsible for the SARS epidemic in 2002 to 2004 and for the more recent coronavirus disease 2019 (Covid-19) pandemic. Why are these viruses infective and how do they differ from the influenza viruses? These viruses respectively, interface with the RAAS (rennin angiotensin aldosterone) through angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically counters RAAS activation also functions as a receptor for both SARS viruses. The interaction between the SARS viruses and ACE2 has been proposed as a potential factor in their infectivity. There are concerns about the use of RAAS inhibitors that may alter ACE2 and whether variation in ACE2 expression may be in part responsible for disease virulence in the ongoing Covid-19 pandemic. Indeed, some media sources and health systems have recently called for the discontinuation of ACE inhibitors and angiotensin-receptor blockers (ARBs), both prophylactically and in the context of suspected Covid-19. Is it possible that ACE2 may be beneficial rather than harmful in patients with lung injury?
Coexisting conditions, including hypertension, have consistently been reported to be more common among patients with Covid-19 who have had severe illness, been admitted to the intensive care unit, received mechanical ventilation, or died than among patients who have had mild illness. There are concerns that medical management of these coexisting conditions, including the use of RAAS inhibitors, may have contributed to the adverse health outcomes observed. However, these conditions appear to track closely with advancing age, which is emerging as the strongest predictor of Covid-19–related death.
ACE2 is a key counterregulatory enzyme that degrades angiotensin II to angiotensin-(1–7), thereby attenuating its effects on vasoconstriction, sodium retention, and fibrosis. Although angiotensin II is the primary substrate of ACE2, that enzyme also cleaves angiotensin I to angiotensin-(1–9) and participates in the hydrolysis of other peptides. In studies in humans, tissue samples from 15 organs have shown that ACE2 is expressed broadly, including in the heart and kidneys, as well as on the principal target cells for SARS-CoV-2, the lung and the alveolar cells. Of interest the role of ACE2 in the lungs appears to be relatively minimal under normal conditions but may be up-regulated in certain clinical states. ACE inhibitors in clinical use do not directly affect ACE2 activity.
SARS-CoV-2 appears not only to gain initial entry through ACE2 but also to subsequently down-regulate ACE2 expression such that the enzyme is unable to exert protective effects in organs. It has been postulated but unproven that unabated angiotensin II activity may be in part responsible for organ injury in Covid-19.
What can be done for a person who falls ill? First keep in mind that the mortality rate is low. Some people like the elderly, the immune compromised, those with other serious underlying diseases should be isolated, observed and cared for with greater intensity. Therapy currently consists of supportive care while a variety of investigational approaches are being explored. Among these are the antiviral medication lopinavir–ritonavir, interferon-1β, the RNA polymerase inhibitor remdesivir, chloroquine, and a variety of traditional Chinese medicine products. Symptomatic relief as needed has to be provided and ventilatory support needs to be available. It is the sudden demand for ICU and ventilatory support which has sent nations scrambling to impose mass isolation, social isolation and the tragic mass migration in India.
We are going to see more outbreaks of diseases related to poverty, malnutrition, emergence of new pathogens as in the wake of the economic disaster which is likely to follow this outbreak. The Covid-19 outbreak should serve as a stark reminder of the ongoing challenge of emerging and reemerging infectious pathogens and the need for constant surveillance, prompt diagnosis, and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures.