Cerami Carla, Rapp Tyler, Lin Feng-Chang, Tompkins Kathleen, Basham Christopher, Muller Meredith S, Whittelsey Maureen, Zhang Haoming, Chhetri Srijana B, Smith Judy, Litel Christy, Lin Kelly, Churiwal Mehal, Khan Salman, Claman Faith, Rubinstein Rebecca, Mollan Katie, Wohl David, Premkumar Lakshmanane, Juliano Jonathan J, Lin Jessica T
Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, The Gambia.
Institute of Global Health and Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC USA.
medRxiv. 2021 Mar 12:2021.03.10.21253173. doi: 10.1101/2021.03.10.21253173.
Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color.
This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05).
SARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance.
美国报告的关于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)家庭内传播的前瞻性研究较少,美国是全球新冠肺炎病例数最多的国家,且疫情对有色人种社区造成了不成比例的影响。
这是一项前瞻性观察性研究。2020年4月至10月期间,北卡罗来纳大学的共同宿主研究(UNC CO-HOST study)在北卡罗来纳州皮埃蒙特地区招募了102名新冠病毒阳性患者及其213名家庭成员,其中45%的人认定为西班牙裔/拉丁裔或非白人。家庭在索引病例出现症状后的中位数6天被纳入研究。家庭内的二代病例通过研究第1天的鼻咽拭子PCR检测以及此后每周的鼻拭子检测(第7天、第14天、第21天)来发现,或者根据第28天的血清学转换来判定。在排除与索引病例同时暴露的家庭接触者后,易感家庭接触者中的二代发病率(SAR)为60%(106/176,95%置信区间53%-67%)。大多数二代病例在研究入组时就已被感染(73/106),而33例是在研究随访期间被观察到的。尽管随着时间推移存在持续暴露和相继传播的可能性,但93%(84/90,95%置信区间86%-97%)的PCR阳性二代病例在索引病例症状出现后的14天内被检测到,而83%在10天内被检测到。入组时鼻咽病毒载量高(>10^6病毒拷贝/微升)的索引病例在研究期间更有可能将病毒传播给家庭接触者(比值比4.9,95%置信区间1.3-18,p=0.02)。此外,家庭内鼻咽病毒载量具有相关性(组内相关系数ICC=0.44,95%置信区间0.26-0.60),这意味着同一家庭中的人更有可能具有相似的病毒载量,提示存在接种物效应。对于居住空间小于6间房且居住人数超过3人的家庭,高家庭居住密度与更高的家庭二代传播风险相关(比值比5.8,95%置信区间1.3-55)(二代发病率=91%,95%置信区间71%-98%)。自我认定为西班牙裔/拉丁裔或非白人的索引病例更有可能居住在高密度环境中并将病毒传播给家庭成员,这使得少数族裔家庭的二代发病率为70%,而白人家庭为52%(p=0.05)。
SARS-CoV-2在家庭成员中传播早且频繁。在居住空间有限且接种量大的家庭中,传播风险及后续发病风险会升高。家庭拥挤导致的极高感染率可能是美国少数族裔中SARS-CoV-2感染发病率和患病率增加的原因。从家庭中首例病例症状出现起进行14天隔离,对于防止家庭内传播是合适的。最终,通过公平分配有效疫苗进行一级预防至关重要。