Respiratory involvement was rare (41). This appears to be a post-infectious phenomenon, as the majority of both pediatric and adult patients had negative RT-PCR studies, but had positive serology for antibodies against SARS- CoV-2 40,41 . The mechanism is not fully understood, but a proposed etiology is endothelial inflammation caused by acute infection which results in immune dysregulation 42 . Other patients who have recovered from COVID-19, develop “postacute COVID-19 syndrome.” Symptoms are typically nonspecific, and most commonly include fatigue and dyspnea. Other symptoms include joint and chest pain as well as “brain fog.” As the SARS-CoV-2 outbreak is relatively new, investigations into better understanding this phenomenon are ongoing 43 . One recently published study by Chaolin Huang and colleagues, followed a cohort of 1733 patients in Wuhan, China, for 6 months following discharge from the hospital for COVID-19 44 . At 6 months post-discharge, the most common symptoms reported by patients were anxiety and depression, sleep disturbances, fatigue, and muscle weakness. Patients who had more severe disease had a higher likelihood of abnormal oxygen diffusion on pulmonary function testing and persistent
second 142 days later, the Nevada patient experienced an increase in symptom severity during his second infection whichoccurred48days after his first infection 48,49 . It is known that neutralizing antibodies are generated in response to COVID-19; however, the durability of this response is not yet known, but is likely within the range of 5-7 months 50, 51 . EMERGENCE OF SARS-CoV-2 VARIANTS Variant strains of SARS-Cov-2 have evolved by mutation during the course of this pandemic. Investigations of these variants will need to address questions regarding transmissibility, virulence, accuracy of diagnostic testing, efficacy of antibody-based treatments and vaccinations, and ability to reinfect individuals with prior infection. One such variant emerged in the UK in the fall of 2020, and is associated with multiple mutations including a spike protein-associated receptor binding domain mutation at position 501 where asparagine has been replaced by tyrosine, i.e., N501Y. The strain is known as B.1.1.7. and it is estimated to be approximately 50% more transmissible than the Wuhan reference strain 52 . This variant may also be associated with an increased risk for severe disease 53 . The UK variant does not appear to have an effect on current vaccine efficacy 54 . However, both currently available vaccine-generated antibodies and COVID-19 antibodies from early natural infections may have decreased efficacy against two additional emerging variants from South Africa (known as B.1.351) and Brazil (known as P.1) due to additional mutations in the spike protein including one at position 484 where glutamic acid is replaced by lysine (i.e., E484K) 55, 56, 57, 58 . By late January 2021, the UK, South African, and Brazilian variants had been detected in the United States. Even with ongoing vaccination efforts, increased vigilance and mitigation measures will be crucial to prevent surges in cases. REFERENCES 1. LeDuc JW, Barry MA. SARS, the first pandemic of the 21st century. Emerg Infect Dis [serial on the Internet]. 2004 Nov [Nov 28 2020] http://dx.doi.org/10.3201/eid1011.040797_02 2. Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev. 2015;28(2):465-522. doi:10.1128/CMR.00102-14 3. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med 2020;382:727-33. DOI: 10.1056/NEJMoa2001017 4. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). https://doi.org/10.1038/ s41586-020-2012-7 5. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region – Case Series. N Engl J Med 2020;382:2012-22. DOI: 10.1056/NEJMoa2004500 6. WHO: WHO Director-General speeches [Internet]. Geneva, 8
abnormalities on high resolution chest CT. MORTALITY AND REINFECTION
As of February 14, 2021, the current case fatality ratio of COVID-19 in the United States is 1.8%, with 148.00 deaths per 100,000 persons 23 . Though numbers of cases and deaths continue to rise, there have been numerous reports that the mortality rate has been decreasing. One study in England confirmed that patients admitted to hospital with COVID-19 in mid-April and May had a significantly lower mortality rate than patients admitted earlier in the pandemic. Their analysis included adjustments for patient demographics and comorbidities which did not seem to account for the change 45 . Proposed reasons for this decline include widespread use of corticosteroids which demonstrated a mortality benefit in the RECOVERY trial 46 , better healthcare provider understanding of the disease process, as well as decreased healthcare burden as mitigation measures have been introduced 45, 47 . Numerous groups around the world are investigating whether this decline is real, or merely due to changes in testing and case reporting, particularly on a country-to-country basis. Confirmed cases of reinfection have been reported. Two such instances are the case of a 33-year-old man in Hong Kong and a 25-year-old man in Nevada. In each case, genomic analysis of the virus isolated from the patient in each infection was performed, and the isolates were genetically distinct. An importance difference between the cases is that while the Hong Kong patient was mildly symptomatic in his first infection and asymptomatic in his
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