Hogmanay 2019 WHO were informed of cluster of cases of Pneumonia of unknown cause in Wuhan city, Hubei province, China.

Novel coronavirus identified, named SARS-CoV-2. COVID19 is associated disease. 75% genetically identical to SARS (severe acute respiratory syndrome) and 50% to MERS (Middle East respiratory syndrome) but of course these are both similarly capable of causing severe disease, whereas many coronaviruses pretty benign. Derived from bat coronavirus, so bats likely to be natural host.

By end of February 2020, more than 70 000 cases reported across China, 2500 fatalities. Pandemic was declared by WHO on 11th March.

Cruise ships including the Diamond Princess in Japan (over 700 cases) and the Zaandaam were particularly hard hit.

Lockdown declared in UK on 23rd March 2020.

5 variants of concern, most recently Omicron.

Risk factors

Spike (s) protein binds to ACE2 receptors, primary role of which is to convert AntiThrombin-II into AT-1,7, controlling heart rate, hypertension, vasoconstriction, sodium retention, oxidative stress, inflammation, and fibrosis, as well as enhancing baroreceptor sensitivity. ACE2 variability across populations potentially explaining particular susceptibility among people with hypertension and Africans (nearly double rate of whites) and Asians (although Indian rates lower than Bangladeshi/Pakistani). Rates among Chinese females actually lower than among Whites! [UK data]

At least 3% of severely affected people have known or previously unrecognised genetic defects in type 1 interferon production (especially TLR3 and IRF7 which amplify production).

Risk of “critical illness “ from COVID-19 RR 1.44 if overweight, 1.97 if obese. UK OpenSAFELY analysis. Death 1.27 if BMI 30-39, 2.27 if BMI>40. ACE-2 higher in obese. Plus different immune responses and challenges to ventilate.

London has double the age standardised mortality of any other part of the UK (Birmingham next), as high as 144 per 100 000 in Newham. Glasgow’s rate is about 80 [UK data].

Diabetes, cancer and poorly controlled asthma associated with death in primary care records study. Residential care homes, health care workers, social deprivation, Black/Asian groups also seem to be particularly at risk of death.

Bronx worse hit than Manhattan, despite similar population density. Higher attack and death rates among Afro-Americans. Role for air pollution too?

Plot of mortality rates by gender/race

Pregnancy increases risk slightly, not much risk to baby although elective preterm delivery may be part of management of sick mother.

Acute neurological presentations in adults, including stroke and Guillain Barre syndrome. Thrombosis risk.

Transmission from asymptomatic cases seems to be less important than symptomatic and pre-symptomatic (1-2 days).

In adults, low lymphocytes, high neutrophils and D-dimer predict mortality.

See Treatment.

COVID in Children

Probably more severe than SARS but still children tend to be less severely affected than adults. Cross protection from immunity from other coronaviruses? Differences in ACE2? Some asymptomatic.

16% of hospitalised children admitted to critical care. Age under 1 yr, or age 10-14 yrs, co-morbidities, black ethnicity are risk factors for critical care admission. Mortality rate less than 1% in hospitalised [Swann, ISARIC study]. 3 PIMS deaths in England, all 10-14yrs. 70% of all COVID related deaths in non-white groups. 24% of deaths had no co-morbidities, 60% had life limiting condition. No deaths in kids with asthma, diabetes, Trisomy 21.

Wheeze uncommon.

X-ray more often negative; CT more sensitive.

Can present with GI symptoms.

One baby born to an infected mother developed severe complications.

Neutrophil and LDH counts go up, lymphocytes go down.

A small series of children with COVID-19 has shown a greater prevalence of peripheral halo (halo-sign) lung consolidations on CT.

The criteria for the definition of Acute Respiratory Distress Syndrome (ARDS) and septic shock, the guidelines for the management of sepsis and septic shock and the use of non-invasive ventilation in children are different from those of adults.

Children desaturate more easily during intubation; therefore, it is important to pre-oxygenate with 100% O2 with a mask with a reservoir before intubating.

A rectal swab may be useful in children to determine the timing of the termination of quarantine.

[Chengdu and Italian experience, from PIPSQC]

WHO supports use of dexamethasone in patients with acute respiratory presentation and hypoxia (sats<90%), tachypnoea, or severe respiratory distress. RECOVERY trial continues to study dexamethasone in neonates, plus roles for azithromycin and toculizimab.

Sotrovimab is first line treatment, Remdesivir second line is licensed in hospitalised patients in oxygen, over 12 years and over 40kg and can be considered in this age group for patients with high-risk comorbidity for non-hospitalised patients also. Treatment should be commenced within 5 days of symptom onset (Sotrovimab), within 7 days of symptom onset (remdesivir). Paxlovid (Nirmatrelvir plus Ritonavir) is alternative first line option in adults.

Paediatric multi inflammatory syndrome associated with COVID19 (PIMS-TS)